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

    Gene ID: 54704, updated on 28-Oct-2024

    Summary

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    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

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    See PDP1 in Genome Data Viewer
    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_000008.11Genomic Context describing neighboring genes Neighboring gene MYL12A pseudogene 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:94886986-94887486 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:94887487-94887987 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr8:94892037-94893236 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27620 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19360 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19361 Neighboring gene MIR378D2 host gene Neighboring gene microRNA 378d-2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19362 Neighboring gene proteasome subunit alpha 2 pseudogene 2 Neighboring gene ribosomal protein L34 pseudogene 18

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • 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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    Related articles in PubMed

    1. Tyr-94 phosphorylation inhibits pyruvate dehydrogenase phosphatase 1 and promotes tumor growth. Shan C, et al. J Biol Chem, 2014 Aug 1. PMID 24962578, Free PMC Article
    2. Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy. Robinson BH, et al. Pediatr Res, 1975 Dec. PMID 172850
    3. Decrease of pyruvate dehydrogenase phosphatase activity in patients with congenital lactic acidemia. Ito M, et al. Clin Chim Acta, 1992 Jul 31. PMID 1327585
    4. Formation of a complex of the catalytic subunit of pyruvate dehydrogenase phosphatase isoform 1 (PDP1c) and the L2 domain forms a Ca2+ binding site and captures PDP1c as a monomer. Turkan A, et al. Biochemistry, 2004 Nov 30. PMID 15554715
    5. Pyruvate dehydrogenase phosphatase deficiency: identification of the first mutation in two brothers and restoration of activity by protein complementation. Maj MC, et al. J Clin Endocrinol Metab, 2005 Jul. PMID 15855260

    See all (58) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. 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.
    2. PDP1 promotes the progression of breast cancer through STAT3 pathway.
      Title: PDP1 promotes the progression of breast cancer through STAT3 pathway.
    3. 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.
    4. 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.
    5. High PDH expression is associated with glucose intolerance.
      Title: Regulation of hepatic pyruvate dehydrogenase phosphorylation in offspring glucose intolerance induced by intrauterine hyperglycemia.
    6. 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.
    7. 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.
    8. 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.
    9. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    10. 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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ32517, FLJ56179, MGC119646

    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 [pyruvate dehydrogenase (acetyl-transferring)]-phosphatase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    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 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
    NP_001155252.1
    NP_001155253.1
    NP_060914.2
    XP_016869077.1
    XP_047277860.1
    XP_047277861.1
    XP_047277862.1
    XP_047277863.1
    XP_047277864.1
    XP_047277865.1
    XP_054216692.1
    XP_054216693.1
    XP_054216694.1
    XP_054216695.1
    XP_054216696.1

    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

    1. NG_012233.1 RefSeqGene

      Range
      4990..14135
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. 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 ...

    2. 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 ...

    3. 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 ...

    4. 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

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      93916923..93926068
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

    2. 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

    3. XM_047421906.1 → XP_047277862.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

      UniProtKB/Swiss-Prot
      B3KX71, J3KPU0, Q5U5K1, Q9P0J1

    4. XM_017013588.2 → XP_016869077.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X1

      UniProtKB/TrEMBL
      B4DYX8

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

      UniProtKB/Swiss-Prot
      B3KX71, J3KPU0, Q5U5K1, Q9P0J1

    6. XM_047421904.1 → XP_047277860.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X2

    7. 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

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      95042005..95051150
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/Swiss-Prot
      B3KX71, J3KPU0, Q5U5K1, Q9P0J1

    2. XM_054360718.1 → XP_054216693.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X2

    3. XM_054360719.1 → XP_054216694.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

      UniProtKB/Swiss-Prot
      B3KX71, J3KPU0, Q5U5K1, Q9P0J1

    4. XM_054360720.1 → XP_054216695.1  pyruvate dehyrogenase phosphatase catalytic subunit 1 isoform X3

      UniProtKB/Swiss-Prot
      B3KX71, J3KPU0, Q5U5K1, Q9P0J1

    5. 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

    1. 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 Accession Links
    GenPept Link UniProtKB Link
    Q9P0J1.3 GenPept UniProtKB/Swiss-Prot:Q9P0J1

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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