PDK3 pyruvate dehydrogenase kinase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PDK3provided by HGNC
Official Full Name: pyruvate dehydrogenase kinase 3provided by HGNC
Primary source: HGNC:HGNC:8811
See related: Ensembl:ENSG00000067992 MIM:300906; AllianceGenome:HGNC:8811
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CMTX6; GS1-358P8.4
Summary: The pyruvate dehydrogenase (PDH) complex is a nuclear-encoded mitochondrial multienzyme complex that catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2). It provides the primary link between glycolysis and the tricarboxylic acid (TCA) cycle, and thus is one of the major enzymes responsible for the regulation of glucose metabolism. The enzymatic activity of PDH is regulated by a phosphorylation/dephosphorylation cycle, and phosphorylation results in inactivation of PDH. The protein encoded by this gene is one of the three pyruvate dehydrogenase kinases that inhibits the PDH complex by phosphorylation of the E1 alpha subunit. This gene is predominantly expressed in the heart and skeletal muscles. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
Expression: Ubiquitous expression in brain (RPKM 5.9), testis (RPKM 4.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp22.11

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (24465286..24550466)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (24049577..24134762)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (24483403..24568583)

Chromosome X - NC_000023.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families.
Title: Unveiling the clinical and electrophysiological profile of CMTX6: Insights from two Brazilian families.
Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model.
Title: Charcot-Marie-tooth disease causing mutation (p.R158H) in pyruvate dehydrogenase kinase 3 (PDK3) affects synaptic transmission, ATP production and causes neurodegeneration in a CMTX6 C. elegans model.
Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.
Title: Overexpression of PDK2 and PDK3 reflects poor prognosis in acute myeloid leukemia.
Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation.
Title: Energy metabolism and mitochondrial defects in X-linked Charcot-Marie-Tooth (CMTX6) iPSC-derived motor neurons with the p.R158H PDK3 mutation.
Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3: Combined spectroscopic and MD simulation studies.
Title: Effect of pH on the structure and function of pyruvate dehydrogenase kinase 3: Combined spectroscopic and MD simulation studies.
miR-497-5p inhibits gastric cancer cell proliferation and growth through targeting PDK3.
Title: miR-497-5p inhibits gastric cancer cell proliferation and growth through targeting PDK3.
PDK3 forms a positive feedback loop with HSF1 to drive glycolysis in chemoresistance.
Title: Metabolic enzyme PDK3 forms a positive feedback loop with transcription factor HSF1 to drive chemoresistance.
The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation.
Title: KDM4A Coactivates E2F1 to Regulate the PDK-Dependent Metabolic Switch between Mitochondrial Oxidation and Glycolysis.
We have identified a p.R158H PDK3 mutation in a Korean X-linked dominant Charcot-Marie-Tooth type 6 family
Title: X-linked Charcot-Marie-Tooth disease type 6 (CMTX6) patients with a p.R158H mutation in the pyruvate dehydrogenase kinase isoenzyme 3 gene.
Accordingly, elevated levels of PDK1, PDK3, and PKM2 and reduced PK activity could be observed in iPSCs and human embryonic stem cells in the undifferentiated state
Title: HIF1α modulates cell fate reprogramming through early glycolytic shift and upregulation of PDK1-3 and PKM2.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Charcot-Marie-Tooth disease X-linked dominant 6 MedGen: C3806702 OMIM: 300905 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH16353 (e-PCR)
- UniSTS:30722

RH17655 (e-PCR)
- UniSTS:82722

SHGC-34422 (e-PCR)
- UniSTS:20519

D8S2279 (e-PCR)
- UniSTS:473907

D1S1425 (e-PCR)
- UniSTS:149621

SHGC-35685 (e-PCR)
- UniSTS:7052

A009V19 (e-PCR)
- UniSTS:21942

DXS8027 (e-PCR), detects polymorphism
- UniSTS:57789

ha2335 (e-PCR)
- UniSTS:515528

G32876 (e-PCR)
- UniSTS:117455

DXS7446E (e-PCR)
- UniSTS:99793

D5S1597E (e-PCR)
- UniSTS:151019

RH45979 (e-PCR)
- UniSTS:55540

Pdk3 (e-PCR), detects polymorphism
- UniSTS:507130

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in cellular response to fatty acid	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hypoxia-inducible factor-1alpha signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peroxisome proliferator activated receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of acetyl-CoA biosynthetic process from pyruvate	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of acetyl-CoA biosynthetic process from pyruvate	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of glucose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of glucose metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of reactive oxygen species metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleolus	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: pyruvate dehydrogenase kinase, isozyme 3

Names: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrial; pyruvate dehydrogenase kinase, isoenzyme 3; pyruvate dehydrogenase, lipoamide, kinase isozyme 3, mitochondrial

NP_001135858.1

EC 2.7.11.2

NP_005382.1

EC 2.7.11.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016762.1 RefSeqGene

Range

5060..74196

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001142386.3 → NP_001135858.1 pyruvate dehydrogenase kinase, isozyme 3 isoform 1 precursor

See identical proteins and their annotated locations for NP_001135858.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AC004656, AI001064, AK301965, BC038512, BI549903, BU069975

Consensus CDS

CCDS48088.1

UniProtKB/Swiss-Prot

Q15120

Related

ENSP00000498864.1, ENST00000568479.2

Conserved Domains (2) summary

cd16929
Location:192 → 359

HATPase_PDK-like; Histidine kinase-like ATPase domain of pyruvate dehydrogenase kinase, branched-chain alpha-ketoacid dehydrogenase kinase and related domains

pfam10436
Location:26 → 188

BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase
NM_005391.5 → NP_005382.1 pyruvate dehydrogenase kinase, isozyme 3 isoform 2 precursor

See identical proteins and their annotated locations for NP_005382.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at the 3' end compared to variant 1, resulting in a shorter isoform (2) lacking the last 9 aa from the C-terminus, compared to isoform 1.

Source sequence(s)

AC004656, BC015948, BI549903, L42452

Consensus CDS

CCDS14212.1

UniProtKB/Swiss-Prot

B4DXG6, Q15120

Related

ENSP00000368460.4, ENST00000379162.9

Conserved Domains (2) summary

smart00387
Location:238 → 359

HATPase_c; Histidine kinase-like ATPases

pfam10436
Location:26 → 188

BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase