PDP1 pyruvate dehyrogenase phosphatase catalytic subunit 1 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PDP1provided by HGNC
Official Full Name: pyruvate dehyrogenase phosphatase catalytic subunit 1provided by HGNC
Primary source: HGNC:9279
See related: Ensembl:ENSG00000164951; HPRD:16185; MIM:605993; Vega:OTTHUMG00000164356
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: PDH; PDP; PDPC; PPM2C
Summary: Pyruvate dehydrogenase (E1) is one of the three components (E1, E2, and E3) of the large pyruvate dehydrogenase complex. Pyruvate dehydrogenase kinases catalyze phosphorylation of serine residues of E1 to inactivate the E1 component and inhibit the complex. Pyruvate dehydrogenase phosphatases catalyze the dephosphorylation and activation of the E1 component to reverse the effects of pyruvate dehydrogenase kinases. Pyruvate dehydrogenase phosphatase is a heterodimer consisting of catalytic and regulatory subunits. Two catalytic subunits have been reported; one is predominantly expressed in skeletal muscle and another one is is much more abundant in the liver. The catalytic subunit, encoded by this gene, is the former, and belongs to the protein phosphatase 2C (PP2C) superfamily. Along with the pyruvate dehydrogenase complex and pyruvate dehydrogenase kinases, this enzyme is located in the mitochondrial matrix. Mutation in this gene causes pyruvate dehydrogenase phosphatase deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Jun 2009]

Genomic context

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Location :: 8q22.1

Sequence :: Chromosome: 8; NC_000008.10 (94929083..94938296)

See PDP1 in Epigenomics, MapViewer

Chromosome 8 - NC_000008.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Although 7 days of bed rest induced whole body glucose intolerance, exercise-induced PDH regulation in skeletal muscle was not changed, suggesting that exercise-induced PDH regulation in skeletal muscle is maintained in glucose-intolerant individuals.
Title: Exercise-induced pyruvate dehydrogenase activation is not affected by 7 days of bed rest.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
catalytic subunit of PDP1 crystals belonged to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 65.1, c = 216.1 A.
Title: Crystallization and preliminary crystallographic studies of the catalytic subunits of human pyruvate dehydrogenase phosphatase isoforms 1 and 2.
pyruvate dehydrogenase phosphatase PDP1 is down-regulated in circulating lymphocytes of obese subjects because it is poorly sensitive to magnesium/calcium; this defect is attenuated when plasma insulin is greatly enhanced
Title: Down-regulation of pyruvate dehydrogenase phosphatase in obese subjects is a defect that signals insulin resistance.
Lower accumulation of free ADP and AMP after the FAT-adapt trial may be responsible for the decreased glycogenolysis and PDH activation during sprinting.
Title: Decreased PDH activation and glycogenolysis during exercise following fat adaptation with carbohydrate restoration.
In cultured skin fibroblasts from three patients with congenital lactic acidemia due to a defect in activation of the pyruvate dehydrogenase complex, the PDP-activity was significantly reduced to 50.7%, 64.6% and 63.1% of that of control fibroblasts.
Title: Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia.
In postmortem tissue samples, from male child with metabolic acidosis, PDK normally reduced PDH-activity in ATP-presence. Addition of Ca++ and Mg++ did not restored PDH-activity. The defect was attributed to a markedly reduced PDP-activity.
Title: Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy.
Functional characterization of the bovine counterpart.
Title: Molecular cloning and expression of the catalytic subunit of bovine pyruvate dehydrogenase phosphatase and sequence similarity with protein phosphatase 2C.
Functional characterization of the rat counterpart.
Title: Isoenzymes of pyruvate dehydrogenase phosphatase. DNA-derived amino acid sequences, expression, and regulation.

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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

Pyruvate dehydrogenase phosphatase deficiency

MIM: 608782

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
Q9P0J1	P08559	PDHA1	HPRD	PubMed
Q9P0J1	Q05655	PRKCD	HPRD	PubMed
BioGRID:120103	BioGRID:111566	PRKCD	BioGRID	PubMed	Affinity Capture-Western
BioGRID:120103	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Pyruvate metabolism, organism-specific biosystem (from REACTOME)
Pyruvate metabolism, organism-specific biosystemPyruvate sits at an intersection of key pathways of energy metabolism. It is the end product of glycolysis and the starting point for gluconeogenesis, and can be generated by transamination of alanin...
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystem (from REACTOME)
Pyruvate metabolism and Citric Acid (TCA) cycle, organism-specific biosystemPyruvate metabolism and the citric acid (TCA) cycle together link the processes of energy metabolism in a human cell with one another and with key biosynthetic reactions. Pyruvate, derived from the r...
Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystem (from REACTOME)
Regulation of pyruvate dehydrogenase (PDH) complex, organism-specific biosystemThe mitochondrial pyruvate dehydrogenase (PDH) complex catalyzes the oxidative decarboxylation of pyruvate, linking glycolysis to the tricarboxylic acid cycle and fatty acid synthesis. PDH inactivati...
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystem (from REACTOME)
The citric acid (TCA) cycle and respiratory electron transport, organism-specific biosystemThe metabolism of pyruvate provides one source of acetyl-CoA which enters the citric acid (TCA, tricarboxylic acid) cycle to generate energy and the reducing equivalent NADH. These reducing equivalen...

General gene information

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Markers

STS-N47861 (e-PCR)
- UniSTS:64541

D8S1599 (e-PCR)
- UniSTS:1082

SHGC-24323 (e-PCR)
- UniSTS:92277

SGC30292 (e-PCR)
- UniSTS:61069

Genotypes

See PDP1 SNP Geneview Report
See PDP1 SNP Genotype Report
See PDP1 SNP Variation Viewer Report

Homology

Homologs of the PDP1 gene: The PDP1 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, and N.crassa.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
[pyruvate dehydrogenase (lipoamide)] phosphatase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info

Process	Evidence Code	Pubs
peptidyl-threonine dephosphorylation	IDA Inferred from Direct Assay more info
pyruvate metabolic process	TAS Traceable Author Statement more info
regulation of acetyl-CoA biosynthetic process from pyruvate	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial matrix	TAS Traceable Author Statement more info

General protein information

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Preferred Names: pyruvate dehyrogenase phosphatase catalytic subunit 1

Names: pyruvate dehyrogenase phosphatase catalytic subunit 1; PDP 1; PDPC 1; pyruvate dehydrogenase phosphatase catalytic subunit 1; pyruvate dehydrogenase (Lipoamide) phosphatase-phosphatase; protein phosphatase 2C, magnesium-dependent, catalytic subunit; [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial

NP_001155251.1

EC 3.1.3.43

NP_001155252.1

EC 3.1.3.43

NP_001155253.1

EC 3.1.3.43

NP_060914.2

EC 3.1.3.43

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_012233.1 RefSeqGene

Range

4922..14135

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001161779.1 → NP_001155251.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) is the longest transcript. This variant and variant 3 encode the same isoform (2).

Source sequence(s)

AK126862, BC098343, BX099681, DA769567

Consensus CDS

CCDS55262.1

UniProtKB/TrEMBL

J3KPU0

UniProtKB/Swiss-Prot

Q9P0J1

Related

ENSP00000379503, ENST00000396200

Conserved Domains (1) summary

cd00143
Location:134 – 465
Blast Score: 391

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
NM_001161780.1 → NP_001155252.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an internal segment in the 5' UTR, compared to variant 2. Variants 2 and 3 encode the same isoform 2.

Source sequence(s)

AK126862, BC064978, BX099681, DA507397

Consensus CDS

CCDS55262.1

UniProtKB/TrEMBL

J3KPU0

UniProtKB/TrEMBL

Q6P1N1

UniProtKB/Swiss-Prot

Q9P0J1

Conserved Domains (1) summary

cd00143
Location:134 – 465
Blast Score: 391

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
NM_001161781.1 → NP_001155253.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an internal exon, compared to variant 2. The difference causes translation initiation at a downstream AUG and results in an isoform (3) with a shorter N-terminus, compared to isoform 2.

Source sequence(s)

AK126862, BX099681, DA240240

Consensus CDS

CCDS6259.1

UniProtKB/Swiss-Prot

Q9P0J1

Conserved Domains (1) summary

cd00143
Location:109 – 440
Blast Score: 390

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
NM_018444.3 → NP_060914.2 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an internal segment, compared to variant 2. The difference causes translation initiation at a downstream AUG and results in an isoform (3) with a shorter N-terminus, compared to isoform 2.

Source sequence(s)

AK126862, BC047619, BX099681, DB084539

Consensus CDS

CCDS6259.1

UniProtKB/Swiss-Prot

Q9P0J1

Related

ENSP00000297598, OTTHUMP00000226523, ENST00000297598, OTTHUMT00000378415

Conserved Domains (1) summary

cd00143
Location:109 – 440
Blast Score: 390

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000008.10 Reference GRCh37.p10 Primary Assembly

Range

94929083..94938296

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000140.1 Alternate HuRef

Range

90137033..90146245

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018919.1 Alternate CHM1_1.0

Range

95085562..95094772

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001161778.1: Suppressed sequence

Description

NM_001161778.1: This RefSeq was permanently suppressed because currently there is support for the transcript but not for the protein.

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01037444.1 (20355..29567)	None
genomic	AC084346.3 (18391..27525)	None
genomic	AMYH01018883.1 (272747..272955)	None
genomic	AMYH01018884.1	None
genomic	CH471060.1	EAW91704.1
		EAW91705.1
		EAW91706.1
mRNA	AF155661.1	AAF67480.1
mRNA	AK022057.1	None
mRNA	AK057079.1	BAG51859.1
mRNA	AK126862.1	BAG54383.1
mRNA	AK302651.1	BAG63890.1
mRNA	AL134195.1	None
mRNA	BC047619.1	AAH47619.1
mRNA	BC064978.1	AAH64978.1
mRNA	BC098343.1	AAH98343.1
mRNA	BM973633.1	None
mRNA	BQ422289.1	None
mRNA	BX099681.1	None
mRNA	DA240240.1	None
mRNA	DA507397.1	None
mRNA	DA769567.1	None
mRNA	DB084539.1	None
mRNA	DC369809.1	None