PCK2 (phosphoenolpyruvate carboxykinase 2, mitochondrial)

Gene

• Entrez ID: 5106
• Gene name: Phosphoenolpyruvate carboxykinase 2, mitochondrial
• Gene symbol: PCK2
• Synonyms (NCBI Gene): PEPCK, PEPCK-M, PEPCK2, mtPCK2
• Chromosome: 14
• Chromosome location: 14q11.2-q12
• 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 glucone

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030573	hsa-miR-24-3p	Microarray	19748357
MIRT031958	hsa-miR-16-5p	Proteomics	18668040
MIRT1217765	hsa-miR-491-3p	CLIP-seq
MIRT1217766	hsa-miR-500a	CLIP-seq
MIRT1217767	hsa-miR-501-3p	CLIP-seq
MIRT1217768	hsa-miR-502-3p	CLIP-seq
MIRT1217769	hsa-miR-183	CLIP-seq
MIRT1217770	hsa-miR-4265	CLIP-seq
MIRT1217771	hsa-miR-4296	CLIP-seq
MIRT1217772	hsa-miR-4322	CLIP-seq
MIRT1217773	hsa-miR-4520a-3p	CLIP-seq
MIRT1217774	hsa-miR-4520b-3p	CLIP-seq
MIRT1217775	hsa-miR-4648	CLIP-seq
MIRT1217776	hsa-miR-4654	CLIP-seq
MIRT1217777	hsa-miR-4699-5p	CLIP-seq
MIRT1217778	hsa-miR-4709-3p	CLIP-seq
MIRT1217779	hsa-miR-4747-5p	CLIP-seq
MIRT1217780	hsa-miR-4769-5p	CLIP-seq
MIRT1217781	hsa-miR-4795-3p	CLIP-seq
MIRT1217782	hsa-miR-493	CLIP-seq
MIRT1217773	hsa-miR-4520a-3p	CLIP-seq
MIRT1217774	hsa-miR-4520b-3p	CLIP-seq
MIRT1217777	hsa-miR-4699-5p	CLIP-seq
MIRT1217778	hsa-miR-4709-3p	CLIP-seq
MIRT1217781	hsa-miR-4795-3p	CLIP-seq
MIRT2291378	hsa-miR-1178	CLIP-seq
MIRT2291379	hsa-miR-1279	CLIP-seq
MIRT2291380	hsa-miR-18a	CLIP-seq
MIRT2291381	hsa-miR-18b	CLIP-seq
MIRT2291382	hsa-miR-2276	CLIP-seq
MIRT2291383	hsa-miR-302f	CLIP-seq
MIRT2291384	hsa-miR-4708-3p	CLIP-seq
MIRT2291385	hsa-miR-4735-3p	CLIP-seq
MIRT2291386	hsa-miR-4761-5p	CLIP-seq
MIRT2291387	hsa-miR-4772-3p	CLIP-seq
MIRT2291388	hsa-miR-544	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ATF2	Unknown	11042264
CEBPA	Unknown	11042264
CEBPB	Activation	8093246
CREBBP	Unknown	10085123;11997389
FOS	Unknown	1325459
HDAC3	Unknown	17456789
JUN	Unknown	1325459
NCOR2	Unknown	17456789
NFIA	Unknown	10085123
NR0B2	Repression	17094771
NR0B2	Unknown	15358835
PPARGC1A	Activation	16891307
RELA	Repression	20137375
SRCAP	Unknown	11522779

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0004611	Function	Phosphoenolpyruvate carboxykinase activity	IEA
GO:0004611	Function	Phosphoenolpyruvate carboxykinase activity	TAS	8645161
GO:0004613	Function	Phosphoenolpyruvate carboxykinase (GTP) activity	EXP	9657976
GO:0004613	Function	Phosphoenolpyruvate carboxykinase (GTP) activity	IBA
GO:0004613	Function	Phosphoenolpyruvate carboxykinase (GTP) activity	IDA	28955899
GO:0004613	Function	Phosphoenolpyruvate carboxykinase (GTP) activity	IEA
GO:0005515	Function	Protein binding	IPI	21988832
GO:0005525	Function	GTP binding	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	8645161
GO:0005739	Component	Mitochondrion	IEA
GO:0005739	Component	Mitochondrion	TAS	8645161
GO:0005759	Component	Mitochondrial matrix	IBA
GO:0005759	Component	Mitochondrial matrix	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0006094	Process	Gluconeogenesis	IBA
GO:0006094	Process	Gluconeogenesis	IEA
GO:0006094	Process	Gluconeogenesis	TAS
GO:0006107	Process	Oxaloacetate metabolic process	IBA
GO:0006107	Process	Oxaloacetate metabolic process	IEA
GO:0016829	Function	Lyase activity	IEA
GO:0016831	Function	Carboxy-lyase activity	IEA
GO:0017076	Function	Purine nucleotide binding	IEA
GO:0019543	Process	Propionate catabolic process	IBA
GO:0030145	Function	Manganese ion binding	IBA
GO:0030145	Function	Manganese ion binding	IDA	28955899
GO:0030145	Function	Manganese ion binding	IEA
GO:0032024	Process	Positive regulation of insulin secretion	IEA
GO:0032496	Process	Response to lipopolysaccharide	IEA
GO:0032869	Process	Cellular response to insulin stimulus	IBA
GO:0042594	Process	Response to starvation	IBA
GO:0046327	Process	Glycerol biosynthetic process from pyruvate	IBA
GO:0046872	Function	Metal ion binding	IEA
GO:0070365	Process	Hepatocyte differentiation	IBA
GO:0071333	Process	Cellular response to glucose stimulus	IBA
GO:0071333	Process	Cellular response to glucose stimulus	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071548	Process	Response to dexamethasone	IEA
GO:0071549	Process	Cellular response to dexamethasone stimulus	IBA

Other IDs

• MIM: 614095
• HGNC: 8725
• e!Ensembl: ENSG00000100889

Protein

• UniProt ID: Q16822
• Protein name: Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (PEPCK-M) (EC 4.1.1.32) (Phosphoenolpyruvate carboxykinase 2, mitochondrial) (mtPCK2)
• Protein function: Mitochondrial phosphoenolpyruvate carboxykinase that catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived fro
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17297	PEPCK_N	46 → 274	Phosphoenolpyruvate carboxykinase N-terminal domain	Domain
  PF00821	PEPCK_GTP	278 → 637	Phosphoenolpyruvate carboxykinase C-terminal P-loop domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9657976}.
• Sequence:

  MAALYRPGLRLNWHGLSPLGWPSCRSIQTLRVLSGDLGQLPTGIRDFVEHSARLCQPEGI
  HICDGTEAENTATLTLLEQQGLIRKLPKYNNCWLARTDPKDVARVESKTVIVTPSQRDTV
  PLPPGGARGQLGNWMSPADFQRAVDERFPGCMQGRTMYVLPFSMGPVGSPLSRIGVQLTD
  SAYVVASMRIMTRLGTPVLQALGDGDFVKCLHSVGQPLTGQGEPVSQWPCNPEKTLIGHV
  PDQREIISFGSGYGGNSLLGKKCFALRIASRLARDEGWLAEHMLILGITSPAGKKRYVAA
  AFPSACGKTNLAMMRPALPGWKVECVGDDIAWMRFDSEGRLRAINPENGFFGVAPGTSAT
  TNPNAMATIQSNTIFTNVAETSDGGVYWEGIDQPLPPGVTVTSWLGKPWKPGDKEPCAHP
  NSRFCAPARQCPIMDPAWEAPEGVPIDAIIFGGRRPKGVPLVYEAFNWRHGVFVGSAMRS
  ESTAAAEHKGKIIMHDPFAMRPFFGYNFGHYLEHWLSMEGRKGAQLPRIFHVNWFRRDEA
  GHFLWPGFGENARVLDWICRRLEGEDSARETPIGLVPKEGALDLSGLRAIDTTQLFSLPK
  DFWEQEVRDIRSYLTEQVNQDLPKEVLAELEALERRVHKM

• Sequence length: 640

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOXIA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PCK2-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PCK2-related neuropathy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Phosphoenolpyruvate carboxykinase (GTP) deficiency	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Phosphoenolpyruvate carboxykinase deficiency, mitochondrial	Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 27	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Autism Spectrum Disorder	Autism	Pubtator	36320054	Associate	★☆☆☆☆ Found in Text Mining only
Bone Diseases	Bone disease	Pubtator	31574189	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	34312289, 35265226, 35580079, 35757841	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	32210020	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	28378759, 31406102, 33893083, 8626491	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	32210020	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	29844165		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	Pubtator	20454521	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	37304670	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	10909974, 11277867, 12916001, 17709878, 7685354		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	10909974, 11277867, 12916001, 17709878, 7685354		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	21726808	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	11334436, 12916001, 16132948, 16620271, 22580743, 30867526, 8547315, 8636258		★☆☆☆☆ Found in Text Mining only
Esophageal Squamous Cell Carcinoma	Esophageal squamous cell carcinoma	Pubtator	33142842	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	BEFREE	15809359		★☆☆☆☆ Found in Text Mining only
Fatty Liver	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	15809359, 23720771		★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	29843131	Inhibit	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	22457523, 31679138, 38102588	Associate	★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	29362600	Stimulate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	36320054	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Acute	Kidney Failure	BEFREE	29357426		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	16126724, 29335519, 30639375, 8626493		★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	16126724, 30639375, 8626493		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	32777161, 34520823	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	29335519		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	29844165		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	29137367		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24973213, 29844165		★☆☆☆☆ Found in Text Mining only
Malnutrition	Malnutrition	BEFREE	28076749		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	28166201		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Metabolic Bone Disorder	Metabolic Bone Disorder	BEFREE	31574189		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic Diseases	BEFREE	31574189		★☆☆☆☆ Found in Text Mining only
Metabolic Diseases	Metabolic syndrome	Pubtator	31574189	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	15809359		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	26474064, 28166201, 29137367		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	26474064		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	30177354		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	30177354	Associate	★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	31205570		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	32878513	Associate	★☆☆☆☆ Found in Text Mining only
Phosphoenolpyruvate carboxykinase 2 deficiency	Phosphoenolpyruvate carboxykinase deficiency	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Phosphoenolpyruvate carboxykinase deficiency	Phosphoenolpyruvate carboxykinase deficiency	ORPHANET_DG	2044592		★☆☆☆☆ Found in Text Mining only
Phosphoenolpyruvate carboxykinase deficiency	Phosphoenolpyruvate carboxykinase deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Phosphoenolpyruvate Carboxykinase Deficiency, Mitochondrial	Phosphoenolpyruvate carboxykinase deficiency	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate carcinoma	Prostate cancer	BEFREE	29137367		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	BEFREE	29137367		★☆☆☆☆ Found in Text Mining only
Rectal Carcinoma	Rectal Carcinoma	BEFREE	24602180		★☆☆☆☆ Found in Text Mining only
Renal steatosis	Renal steatosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	BEFREE	15809359, 18316359		★☆☆☆☆ Found in Text Mining only
Steatohepatitis	Fatty Liver	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	30380689	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple negative breast cancer	Pubtator	35757841	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	26299484	Associate	★☆☆☆☆ Found in Text Mining only