Pdk2 pyruvate dehydrogenase kinase, isoenzyme 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Pdk2provided by MGI
Official Full Name: pyruvate dehydrogenase kinase, isoenzyme 2provided by MGI
Primary source: MGI:MGI:1343087
See related: Ensembl:ENSMUSG00000038967 AllianceGenome:MGI:1343087
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables pyruvate dehydrogenase (acetyl-transferring) kinase activity. Involved in several processes, including insulin receptor signaling pathway; regulation of acetyl-CoA biosynthetic process from pyruvate; and regulation of gluconeogenesis. Acts upstream of or within regulation of calcium-mediated signaling. Located in mitochondrion. Part of mitochondrial pyruvate dehydrogenase complex. Is expressed in heart. Orthologous to human PDK2 (pyruvate dehydrogenase kinase 2). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in heart adult (RPKM 156.0), kidney adult (RPKM 138.3) and 19 other tissues See more
Orthologs: human all
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Genomic context

Location:: 11 D; 11 59.01 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (94917084..94932197, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (95026258..95041371, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation.
Title: Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation.
Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes.
Title: Pyruvate dehydrogenase kinase 1 and 2 deficiency reduces high-fat diet-induced hypertrophic obesity and inhibits the differentiation of preadipocytes into mature adipocytes.
PDK2 Deficiency Prevents Ovariectomy-Induced Bone Loss in Mice by Regulating the RANKL-NFATc1 Pathway During Osteoclastogenesis.
Title: PDK2 Deficiency Prevents Ovariectomy-Induced Bone Loss in Mice by Regulating the RANKL-NFATc1 Pathway During Osteoclastogenesis.
Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype.
Title: Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype.
our results suggest that PDK2/4 can be a potential target for the development of pharmacotherapy for the treatment of acute inflammatory pain
Title: Pyruvate dehydrogenase kinase 2 and 4 gene deficiency attenuates nociceptive behaviors in a mouse model of acute inflammatory pain.
The current study reports that increasing hepatic PDC activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease.
Title: Inhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis.
PDK2/4 induction and the subsequent lactate surge induce the metabolic shift in the diabetic dorsal root ganglion thereby contributing to the pathogenesis of painful diabetic neuropathy.
Title: Pyruvate Dehydrogenase Kinase-mediated Glycolytic Metabolic Shift in the Dorsal Root Ganglion Drives Painful Diabetic Neuropathy.
These findings reveal that there are divergent roles of PDKs during oocyte maturation and indicate a new mechanism controlling meiotic structure.
Title: Differing roles of pyruvate dehydrogenase kinases during mouse oocyte maturation.
Double-knockout mice with global deletion of PDK2 and PDK4, which results in constitutively activated pyruvate dehydrogenase, preferentially oxidize glucose in muscle.
Title: Genetic activation of pyruvate dehydrogenase alters oxidative substrate selection to induce skeletal muscle insulin resistance.
The final compound of this series, 2-[(2,4-dihydroxyphenyl)sulfonyl]isoindoline-4,6-diol, designated PS10, inhibits all four PDK isoforms with IC50 = 0.8 muM for PDK2.
Title: Structure-guided development of specific pyruvate dehydrogenase kinase inhibitors targeting the ATP-binding pocket.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (2) 1 citation
Endonuclease-mediated (4)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Pdk2 (e-PCR), detects polymorphism
- UniSTS:144155

MARC_7915-7916:996688163:1 (e-PCR)
- UniSTS:269854

AI854782 (e-PCR)
- UniSTS:180296

Pdk2 (e-PCR), detects polymorphism
- UniSTS:527483

NoName (e-PCR)
- UniSTS:236707

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables pyruvate dehydrogenase (acetyl-transferring) kinase activity	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cellular response to nutrient	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to reactive oxygen species	ISO Inferred from Sequence Orthology more info
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in insulin receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein phosphorylation	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
acts_upstream_of_or_within regulation of calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cellular ketone metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of gluconeogenesis	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 pH	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	HDA 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	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
part_of pyruvate dehydrogenase complex	IDA Inferred from Direct Assay more info	PubMed
part_of pyruvate dehydrogenase complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: pyruvate dehydrogenase kinase, isoenzyme 2

Names: PDH kinase 2; [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 2, mitochondrial; [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial; pyruvate dehydrogenase 2; pyruvate dehydrogenase kinase, isozyme 2

NP_001348844.1

EC 2.7.11.2

NP_598428.2

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.

mRNA and Protein(s)

NM_001361915.1 → NP_001348844.1 pyruvate dehydrogenase kinase, isoenzyme 2 isoform 2

Status: VALIDATED

Source sequence(s)

AI848783, BE647354, CK618575, CN538500, CX204954, CX208144

Conserved Domains (2) summary

cd16929
Location:132 → 297

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

pfam10436
Location:1 → 128

BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase
NM_133667.2 → NP_598428.2 pyruvate dehydrogenase kinase, isoenzyme 2 isoform 1

See identical proteins and their annotated locations for NP_598428.2

Status: VALIDATED

Source sequence(s)

AF267660, AI848783, CK618575, CX204954, CX223857

Consensus CDS

CCDS25270.1

UniProtKB/Swiss-Prot

Q8VC63, Q9JK42

Related

ENSMUSP00000041447.8, ENSMUST00000038431.8

Conserved Domains (2) summary

pfam10436
Location:30 → 192

BCDHK_Adom3; Mitochondrial branched-chain alpha-ketoacid dehydrogenase kinase

cd16929
Location:196 → 361

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