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    PCK2 phosphoenolpyruvate carboxykinase 2, mitochondrial [ Homo sapiens (human) ]

    Gene ID: 5106, updated on 10-Dec-2024

    Summary

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    Official Symbol
    PCK2provided by HGNC
    Official Full Name
    phosphoenolpyruvate carboxykinase 2, mitochondrialprovided by HGNC
    Primary source
    HGNC:HGNC:8725
    See related
    Ensembl:ENSG00000100889 MIM:614095; AllianceGenome:HGNC:8725
    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
    PEPCK; PEPCK2; mtPCK2; PEPCK-M
    Summary
    This gene encodes a mitochondrial enzyme that catalyzes the conversion of oxaloacetate to phosphoenolpyruvate in the presence of guanosine triphosphate (GTP). A cytosolic form of this protein is encoded by a different gene and is the key enzyme of gluconeogenesis in the liver. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2014]
    Expression
    Biased expression in duodenum (RPKM 127.7), small intestine (RPKM 91.2) and 8 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See PCK2 in Genome Data Viewer
    Location:
    14q11.2-q12
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (24094171..24104125)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (18292333..18302437)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (24563520..24573334)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene capping protein regulator and myosin 1 linker 3 Neighboring gene uncharacterized LOC105370412 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8184 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:24544925-24546124 Neighboring gene copine 6 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8185 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5620 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5621 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:24551461-24552375 Neighboring gene neural retina leucine zipper Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:24558209-24558708 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8186 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5622 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:24563543-24564192 Neighboring gene Sharpr-MPRA regulatory region 2696 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:24583239-24583954 Neighboring gene DDB1 and CUL4 associated factor 11 Neighboring gene fat storage inducing transmembrane protein 1

    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
    • 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. Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth. Vincent EE, et al. Mol Cell, 2015 Oct 15. PMID 26474064
    2. Low expression of PCK2 in breast tumors contributes to better prognosis by inducing senescence of cancer cells. Ma X, et al. IUBMB Life, 2022 Sep. PMID 35580079
    3. A novel mutation in PCK2 gene causes primary angle-closure glaucoma. Xu M, et al. Aging (Albany NY), 2021 Oct 14. PMID 34650006, Free PMC Article
    4. PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells. Bluemel G, et al. Free Radic Biol Med, 2021 Nov 20. PMID 34520823
    5. Restoring the epigenetically silenced PCK2 suppresses renal cell carcinoma progression and increases sensitivity to sunitinib by promoting endoplasmic reticulum stress. Xiong Z, et al. Theranostics, 2020. PMID 33052225, Free PMC Article

    See all (104) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.
      Title: Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.
    2. Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma.
      Title: Association of mitochondrial phosphoenolpyruvate carboxykinase with prognosis and immune regulation in hepatocellular carcinoma.
    3. Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis.
      Title: Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis.
    4. AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription.
      Title: AF9 sustains glycolysis in colorectal cancer via H3K9ac-mediated PCK2 and FBP1 transcription.
    5. Mitochondrial phosphoenolpyruvate carboxykinase promotes tumor growth in estrogen receptor-positive breast cancer via regulation of the mTOR pathway.
      Title: Mitochondrial phosphoenolpyruvate carboxykinase promotes tumor growth in estrogen receptor-positive breast cancer via regulation of the mTOR pathway.
    6. Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells.
      Title: Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells.
    7. Low expression of PCK2 in breast tumors contributes to better prognosis by inducing senescence of cancer cells.
      Title: Low expression of PCK2 in breast tumors contributes to better prognosis by inducing senescence of cancer cells.
    8. Role of PCK2 in the proliferation of vascular smooth muscle cells in neointimal hyperplasia.
      Title: Role of PCK2 in the proliferation of vascular smooth muscle cells in neointimal hyperplasia.
    9. A novel mutation in PCK2 gene causes primary angle-closure glaucoma.
      Title: A novel mutation in PCK2 gene causes primary angle-closure glaucoma.
    10. Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
      Title: Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
    Submit: New GeneRIF Correction See all GeneRIFs (35)

    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
    Phosphoenolpyruvate carboxykinase deficiency, mitochondrial
    MedGen: C1849821 OMIM: 261650 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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    matrix gag HIV-1 MA increases PCK2 mRNA expression in HepG2 cells PubMed

    Go to the HIV-1, Human Interaction Database

    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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables GTP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables manganese ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables manganese ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphoenolpyruvate carboxykinase (GTP) activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables phosphoenolpyruvate carboxykinase (GTP) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables phosphoenolpyruvate carboxykinase (GTP) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables phosphoenolpyruvate carboxykinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NADH oxidation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in cellular response to dexamethasone stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to glucose stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to insulin stimulus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in cellular response to tumor necrosis factor IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gluconeogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in gluconeogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gluconeogenesis TAS
    Traceable Author Statement
    more info
    		  
    involved_in glycerol biosynthetic process from pyruvate IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in hepatocyte differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in oxaloacetate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of insulin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in propionate catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in response to starvation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Component Evidence Code Pubs
    is_active_in mitochondrial matrix IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    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 

    General protein information

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    Preferred Names
    phosphoenolpyruvate carboxykinase [GTP], mitochondrial
    Names
    PEP carboxykinase
    epididymis secretory sperm binding protein
    phosphopyruvate carboxylase
    NP_001018083.2
    NP_001278485.1
    NP_001294983.1
    NP_004554.3
    XP_006720221.1
    XP_047287384.1
    XP_047287385.1
    XP_054188324.1
    XP_054188325.1
    XP_054232136.1
    XP_054232137.1
    XP_054232138.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_008162.2 RefSeqGene

      Range
      5038..14852
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001018073.3 → NP_001018083.2  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks multiple 3' coding exons and its 3' terminal exon extends past a splice site used in the variant 1, resulting in a different 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AL136295, BX248272, CN359636, DB028389, KF455834
      Consensus CDS
      CCDS41928.1
      UniProtKB/TrEMBL
      A0A0S2Z451
      Related
      ENSP00000380171.4, ENST00000396973.8
      Conserved Domains (1) summary
      cl22860
      Location:44 → 412
      PEPCK_HprK; Phosphoenolpyruvate carboxykinase (PEPCK), a critical gluconeogenic enzyme, catalyzes the first committed step in the diversion of tricarboxylic acid cycle intermediates toward gluconeogenesis. It catalyzes the reversible decarboxylation and ...

    2. NM_001291556.2 → NP_001278485.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001278485.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate exon and lacks an exon in the 5' region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus than isoform 1. Variants 3 and 4 encode the same isoform.
      Source sequence(s)
      AK129934, AK316206, DB028389
      Consensus CDS
      CCDS76660.1
      UniProtKB/TrEMBL
      H0YML5
      Related
      ENSP00000454011.1, ENST00000561286.5
      Conserved Domains (1) summary
      cd00819
      Location:1 → 499
      PEPCK_GTP; Phosphoenolpyruvate carboxykinase (PEPCK), a critical gluconeogenic enzyme, catalyzes the first committed step in the diversion of tricarboxylic acid cycle intermediates toward gluconeogenesis. It catalyzes the reversible decarboxylation and ...

    3. NM_001308054.2 → NP_001294983.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform 3

      See identical proteins and their annotated locations for NP_001294983.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and uses an alternate 5'-terminal exon, which results in use of a downstream in-frame start codon compared to variant 1. It encodes isoform 3, which has a shorter N-terminus than isoform 1. Variants 3 and 4 encode the same isoform.
      Source sequence(s)
      AK301400, BQ957219, BU153045, CA444720, DA645036
      Consensus CDS
      CCDS76660.1
      UniProtKB/TrEMBL
      H0YML5
      Related
      ENSP00000441826.2, ENST00000545054.6
      Conserved Domains (1) summary
      cd00819
      Location:1 → 499
      PEPCK_GTP; Phosphoenolpyruvate carboxykinase (PEPCK), a critical gluconeogenic enzyme, catalyzes the first committed step in the diversion of tricarboxylic acid cycle intermediates toward gluconeogenesis. It catalyzes the reversible decarboxylation and ...

    4. NM_004563.4 → NP_004554.3  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform 1 precursor

      See identical proteins and their annotated locations for NP_004554.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AK129934, DB028389
      Consensus CDS
      CCDS9609.1
      UniProtKB/Swiss-Prot
      B4DW73, O43253, Q16822, Q86U01, Q9BV62
      UniProtKB/TrEMBL
      A0A0S2Z430, A0A384MTT2
      Related
      ENSP00000216780.4, ENST00000216780.9
      Conserved Domains (1) summary
      cd00819
      Location:44 → 633
      PEPCK_GTP; Phosphoenolpyruvate carboxykinase (PEPCK), a critical gluconeogenic enzyme, catalyzes the first committed step in the diversion of tricarboxylic acid cycle intermediates toward gluconeogenesis. It catalyzes the reversible decarboxylation and ...

    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_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      24094171..24104125
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047431429.1 → XP_047287385.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1

      UniProtKB/TrEMBL
      H0YML5

    2. XM_047431428.1 → XP_047287384.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1

      UniProtKB/TrEMBL
      H0YML5

    3. XM_006720158.3 → XP_006720221.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z451
      Related
      ENSP00000453444.1, ENST00000559250.5
      Conserved Domains (1) summary
      cd00819
      Location:44 → 490
      PEPCK_GTP; Phosphoenolpyruvate carboxykinase (PEPCK), a critical gluconeogenic enzyme, catalyzes the first committed step in the diversion of tricarboxylic acid cycle intermediates toward gluconeogenesis. It catalyzes the reversible decarboxylation and ...

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654722.1 Reference GRCh38.p14 PATCHES

      Range
      395154..405103
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054332349.1 → XP_054188324.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1

      UniProtKB/TrEMBL
      H0YML5

    2. XM_054332350.1 → XP_054188325.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z451

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      18292333..18302437
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376162.1 → XP_054232137.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1

      UniProtKB/TrEMBL
      H0YML5

    2. XM_054376161.1 → XP_054232136.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X1

      UniProtKB/TrEMBL
      H0YML5

    3. XM_054376163.1 → XP_054232138.1  phosphoenolpyruvate carboxykinase [GTP], mitochondrial isoform X2

      UniProtKB/TrEMBL
      A0A0S2Z451
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16822.4 GenPept UniProtKB/Swiss-Prot:Q16822

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