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

Gene ID: 5106, updated on 11-Apr-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
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Genomic context

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Location:
14q11.2-q12
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (24094171..24104125)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (18292333..18302437)
105.20220307 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. Glycosylation defects, offset by PEPCK-M, drive entosis in breast carcinoma cells. Hyroššová P, et al. Cell Death Dis, 2022 Aug 24. PMID 36002449, Free PMC Article
  2. Mitochondrial phosphoenolpyruvate carboxykinase promotes tumor growth in estrogen receptor-positive breast cancer via regulation of the mTOR pathway. Hsu HP, et al. Cancer Med, 2023 Jan. PMID 35757841, Free PMC Article
  3. 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
  4. 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
  5. 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

See all (92) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. A novel mutation in PCK2 gene causes primary angle-closure glaucoma.
    Title: A novel mutation in PCK2 gene causes primary angle-closure glaucoma.
  7. Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
    Title: Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
  8. PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells.
    Title: PCK2 opposes mitochondrial respiration and maintains the redox balance in starved lung cancer cells.
  9. Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2.
    Title: Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2.
  10. PURalpha Promotes the Transcriptional Activation of PCK2 in Oesophageal Squamous Cell Carcinoma Cells.
    Title: PURα Promotes the Transcriptional Activation of PCK2 in Oesophageal Squamous Cell Carcinoma Cells.
Submit: New GeneRIF Correction See all GeneRIFs (32)

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
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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

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 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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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_2023_10

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

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

  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

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

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

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

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

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

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