PCK1 phosphoenolpyruvate carboxykinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PCK1provided by HGNC
Official Full Name: phosphoenolpyruvate carboxykinase 1provided by HGNC
Primary source: HGNC:HGNC:8724
See related: Ensembl:ENSG00000124253 MIM:614168; AllianceGenome:HGNC:8724
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: PCKDC; PEPCK1; PEPCKC; PEPCK-C
Summary: This gene is a main control point for the regulation of gluconeogenesis. The cytosolic enzyme encoded by this gene, along with GTP, catalyzes the formation of phosphoenolpyruvate from oxaloacetate, with the release of carbon dioxide and GDP. The expression of this gene can be regulated by insulin, glucocorticoids, glucagon, cAMP, and diet. Defects in this gene are a cause of cytosolic phosphoenolpyruvate carboxykinase deficiency. A mitochondrial isozyme of the encoded protein also has been characterized. [provided by RefSeq, Jul 2008]
Expression: Biased expression in liver (RPKM 471.7), kidney (RPKM 448.1) and 4 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q13.31

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (57561110..57568121)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (59338907..59345912)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (56136166..56143177)

Chromosome 20 - NC_000020.11 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis.
Title: Dysregulation of phosphoenolpyruvate carboxykinase in cancers: A comprehensive analysis.
Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis.
Title: Upregulation of p300 in paclitaxel-resistant TNBC: implications for cell proliferation via the PCK1/AMPK axis.
Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families.
Title: Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families.
Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction.
Title: Suppression of SLC39A6-CREB1 axis in liver cancer causes PCK1-mediated mitochondrial dysfunction.
Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression.
Title: Gluconeogenic enzyme PCK1 supports S-adenosylmethionine biosynthesis and promotes H3K9me3 modification to suppress hepatocellular carcinoma progression.
MiR-93-5P Represses the Gluconeogenesis of Hepatocellular Carcinoma while Boosting Its Glycolysis and Malignant Progression by Suppressing PCK1.
Title: MiR-93-5P Represses the Gluconeogenesis of Hepatocellular Carcinoma while Boosting Its Glycolysis and Malignant Progression by Suppressing PCK1.
Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
Title: Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.
PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer.
Title: PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer.
Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation.
Title: Gluconeogenic enzyme PCK1 deficiency promotes CHK2 O-GlcNAcylation and hepatocellular carcinoma growth upon glucose deprivation.
Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity.
Title: Self-acetylation at the active site of phosphoenolpyruvate carboxykinase (PCK1) controls enzyme activity.

Submit: New GeneRIF Correction See all GeneRIFs (61)

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, cytosolic MedGen: C5574905 OMIM: 261680 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. EBI GWAS Catalog EBI GWAS CatalogPubMed
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interaction	Pubs
Knockdown of phosphoenolpyruvate carboxykinase 1 (PCK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein	Gene	Interaction	Pubs
integrase	gag-pol	Interaction of human PCK1 with HIV-1 integrase is presumed based on a reported binding interaction between yeast PCK1 and integrase	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH64136 (e-PCR)
- UniSTS:25176

Pck1 (e-PCR), detects polymorphism
- UniSTS:461927

SHGC-1372 (e-PCR)
- UniSTS:29838

D20S1148 (e-PCR)
- UniSTS:41692

SHGC-35332 (e-PCR)
- UniSTS:11485

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables carboxy-lyase activity	IEA Inferred from Electronic Annotation more info
enables carboxylic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables lyase activity	IEA Inferred from Electronic Annotation more info
enables magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
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 manganese ion binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
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 (GTP) activity	IEA Inferred from Electronic Annotation more info
enables phosphoenolpyruvate carboxykinase (GTP) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables phosphoenolpyruvate carboxykinase (GTP) activity	ISS Inferred from Sequence or Structural Similarity more info
enables phosphoenolpyruvate carboxykinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine kinase activity (using GTP as donor)	IDA Inferred from Direct Assay more info	PubMed
enables protein serine kinase activity (using GTP as donor)	IEA Inferred from Electronic Annotation more info
enables purine nucleotide binding	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within NLS-bearing protein import into nucleus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within NLS-bearing protein import into nucleus	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within SREBP-SCAP complex retention in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
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 glucose stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to insulin stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to insulin stimulus	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to potassium ion starvation	IEA Inferred from Electronic Annotation more info
involved_in dicarboxylic acid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in gluconeogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in gluconeogenesis	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within gluconeogenesis	IEA Inferred from Electronic Annotation more info
involved_in gluconeogenesis	IEA Inferred from Electronic Annotation more info
involved_in gluconeogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in gluconeogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in gluconeogenesis	TAS Traceable Author Statement more info
involved_in glucose homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glyceraldehyde-3-phosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in glycerol biosynthetic process from pyruvate	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within glycerol biosynthetic process from pyruvate	IEA Inferred from Electronic Annotation more info
involved_in glycerol biosynthetic process from pyruvate	ISS Inferred from Sequence or Structural Similarity more info
involved_in hepatocyte differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in oxaloacetate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in oxaloacetate metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in oxaloacetate metabolic process	IEA Inferred from Electronic Annotation more info
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lipid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of memory T cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of memory T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
involved_in propionate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within protein maturation	EXP Inferred from Experiment more info	PubMed
acts_upstream_of_or_within protein maturation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within protein maturation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lipid biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in response to insulin	IDA Inferred from Direct Assay more info	PubMed
involved_in response to starvation	IBA Inferred from Biological aspect of Ancestor more info
involved_in tricarboxylic acid metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: phosphoenolpyruvate carboxykinase, cytosolic [GTP]

Names: PEP carboxykinase; phosphoenolpyruvate carboxykinase 1 (soluble); phosphoenolpyruvate carboxykinase, cytosolic; phosphoenolpyruvate carboxylase; phosphopyruvate carboxylase; serine-protein kinase PCK1

NP_002582.3

EC 4.1.1.32

XP_024307656.1

EC 4.1.1.32

XP_054179443.1

EC 4.1.1.32

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_008205.1 RefSeqGene

Range

5030..12041

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002591.4 → NP_002582.3 phosphoenolpyruvate carboxykinase, cytosolic [GTP]

See identical proteins and their annotated locations for NP_002582.3

Status: REVIEWED

Source sequence(s)

AL035541, AW007566, BC023978, BJ993061, BM758256, DB187814

Consensus CDS

CCDS13460.1

UniProtKB/Swiss-Prot

A8K437, B4DT64, P35558, Q8TCA3, Q9UJD2

Related

ENSP00000319814.4, ENST00000319441.6

Conserved Domains (1) summary

cd00819
Location:27 → 615

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

NC_000020.11 Reference GRCh38.p14 Primary Assembly

Range

57561110..57568121

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024451888.2 → XP_024307656.1 phosphoenolpyruvate carboxykinase, cytosolic [GTP] isoform X1

Conserved Domains (1) summary

cd00819
Location:4 → 483

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 ...