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

Summary

Official Symbol: PDP1provided by HGNC
Official Full Name: pyruvate dehydrogenase phosphatase catalytic subunit 1provided by HGNC
Primary source: HGNC:HGNC:9279
See related: Ensembl:ENSG00000164951 MIM:605993; AllianceGenome:HGNC:9279
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; PPM2A; PPM2C; PDPC 1
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]
Expression: Broad expression in adrenal (RPKM 28.1), brain (RPKM 24.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q22.1

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (93916923..93926068)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (95042005..95051150)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (94929151..94938296)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1.
Title: PDP1 promotes KRAS mutant colorectal cancer progression by serving as a scaffold for BRAF and MEK1.
PDP1 promotes the progression of breast cancer through STAT3 pathway.
Title: PDP1 promotes the progression of breast cancer through STAT3 pathway.
PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia.
Title: PDP1 is a key metabolic gatekeeper and modulator of drug resistance in FLT3-ITD-positive acute myeloid leukemia.
Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca(2+)]m-PDP1-PDH-histone acetylation retrograde signaling.
Title: Mitochondrial dysfunction induces radioresistance in colorectal cancer by activating [Ca(2+)](m)-PDP1-PDH-histone acetylation retrograde signaling.
High PDH expression is associated with glucose intolerance.
Title: Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia.
YB-1 phosphorylation at Ser-102 is an important prerequisite for CCL5 promoter activation during macrophage differentiation
Title: Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth.
the pyruvate dehydrogenase complex is regulated by Tyr phosphorylation of PDP1, which toggles recruitment between ACAT1 and SIRT3
Title: Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex.
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.

Submit: New GeneRIF Correction See all GeneRIFs (16)

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
Pyruvate dehydrogenase phosphatase deficiency MedGen: C1837429 OMIM: 608782 GeneReviews: Primary Pyruvate Dehydrogenase Complex Deficiency Overview	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

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

D8S1599 (e-PCR)
- UniSTS:1082

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

SGC30292 (e-PCR)
- UniSTS:61069

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in peptidyl-threonine dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

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	PubMed
located_in mitochondrion	NAS Non-traceable Author Statement more info	PubMed
part_of pyruvate dehydrogenase (lipoamide) phosphatase complex	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: pyruvate dehyrogenase phosphatase catalytic subunit 1

Names: [Pyruvate dehydrogenase [acetyl-transferring]]-phosphatase 1, mitochondrial; protein phosphatase 2C, magnesium-dependent, catalytic subunit; protein phosphatase, Mg2+/Mn2+ dependent 2A; pyruvate dehydrogenase (Lipoamide) phosphatase-phosphatase

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

XP_016869077.1

EC 3.1.3.43

XP_047277860.1

EC 3.1.3.43

XP_047277861.1

EC 3.1.3.43

XP_047277862.1

EC 3.1.3.43

XP_047277863.1

EC 3.1.3.43

XP_047277864.1

EC 3.1.3.43

XP_047277865.1

EC 3.1.3.43

XP_054216692.1

EC 3.1.3.43

XP_054216693.1

EC 3.1.3.43

XP_054216694.1

EC 3.1.3.43

XP_054216695.1

EC 3.1.3.43

XP_054216696.1

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

4990..14135

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for NP_001155251.1

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)

AC084346, AK126862, BC098343, BX099681, DA769567

Consensus CDS

CCDS55262.1

UniProtKB/TrEMBL

B4DYX8

Related

ENSP00000379503.3, ENST00000396200.3

Conserved Domains (1) summary

cd00143
Location:134 → 550

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_001161780.2 → NP_001155252.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 2

See identical proteins and their annotated locations for NP_001155252.1

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)

AC084346, AK126862, BC064978, BX099681, DA507397

Consensus CDS

CCDS55262.1

UniProtKB/TrEMBL

B4DYX8

Conserved Domains (1) summary

cd00143
Location:134 → 550

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_001161781.2 → NP_001155253.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 3

See identical proteins and their annotated locations for NP_001155253.1

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)

AC084346, AK126862, BX099681, DA240240

Consensus CDS

CCDS6259.1

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1

UniProtKB/TrEMBL

B3KPZ7

Conserved Domains (1) summary

cd00143
Location:109 → 525

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_018444.4 → NP_060914.2 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform 3

See identical proteins and their annotated locations for NP_060914.2

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

B3KX71, J3KPU0, Q5U5K1, Q9P0J1

UniProtKB/TrEMBL

B3KPZ7

Related

ENSP00000297598.4, ENST00000297598.5

Conserved Domains (1) summary

cd00143
Location:109 → 525

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: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

93916923..93926068

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047421905.1 → XP_047277861.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X2
XM_047421907.1 → XP_047277863.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1

Related

ENSP00000428317.1, ENST00000520728.5
XM_047421906.1 → XP_047277862.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1
XM_017013588.2 → XP_016869077.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X1

UniProtKB/TrEMBL

B4DYX8
XM_047421909.1 → XP_047277865.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1
XM_047421904.1 → XP_047277860.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X2
XM_047421908.1 → XP_047277864.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1

Related

ENSP00000430380.1, ENST00000517764.1

Alternate T2T-CHM13v2.0

Genomic

NC_060932.1 Alternate T2T-CHM13v2.0

Range

95042005..95051150

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054360721.1 → XP_054216696.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1
XM_054360718.1 → XP_054216693.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X2
XM_054360719.1 → XP_054216694.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1
XM_054360720.1 → XP_054216695.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

UniProtKB/Swiss-Prot

B3KX71, J3KPU0, Q5U5K1, Q9P0J1
XM_054360717.1 → XP_054216692.1 pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X1

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.