PC pyruvate carboxylase [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PCprovided by HGNC
Official Full Name: pyruvate carboxylaseprovided by HGNC
Primary source: HGNC:8636
See related: Ensembl:ENSG00000173599; HPRD:02032; MIM:608786; Vega:OTTHUMG00000167099
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: PCB
Summary: This gene encodes pyruvate carboxylase, which requires biotin and ATP to catalyse the carboxylation of pyruvate to oxaloacetate. The active enzyme is a homotetramer arranged in a tetrahedron which is located exclusively in the mitochondrial matrix. Pyruvate carboxylase is involved in gluconeogenesis, lipogenesis, insulin secretion and synthesis of the neurotransmitter glutamate. Mutations in this gene have been associated with pyruvate carboxylase deficiency. Alternatively spliced transcript variants with different 5' UTRs, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 11q13.4-q13.5

Sequence :: Chromosome: 11; NC_000011.9 (66615997..66725847, complement)

See PC in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

PC protein is easily detectable by streptavidin blot and the presence of considerable amounts of PC in cultured human myotubes and in human muscle tissue was shown.
Title: Pyruvate carboxylase is expressed in human skeletal muscle.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
Nine novel mutations of the PC gene, in five unrelated patients, are reported.
Title: Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency.
The activities of pyruvate carboxylase (PC) were decreased by 65% in pancreatic islets of patients with type 2 diabetes.
Title: Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes.
Eight novel mutations were identified in PC from 8 pyruvate carboxylase deficiency patients.
Title: The molecular basis of pyruvate carboxylase deficiency: mosaicism correlates with prolonged survival.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: Thrombophilia and unexplained pregnancy loss in Indian patients.
The crystal structures at 2.8-A resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC, is reported.
Title: Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.
IVS15+2-5delTAGG results in the retention of intron 15 during pre-mRNA splicing and frameshift mutations.
Title: Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings.
1 deficiency patient survived from neonatal lactic acidemia and shows an unusual subcortical leucodystrophic process.
Title: A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation.
expression and characterization of a variant by retroviral gene transfer
Title: Expression and characterization of a human pyruvate carboxylase variant by retroviral gene transfer.

Submit: New GeneRIF Correction

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

Pyruvate carboxylase deficiency

MIM: 266150

Genetic Testing Registry

Summary from GeneReviews: Pyruvate Carboxylase Deficiency

Pyruvate carboxylase (PC) deficiency is characterized in most affected individuals by failure to thrive, developmental delay, recurrent seizures, and metabolic acidosis. Three clinical types are recognized: type A (infantile form), in which most affected children die in infancy or early childhood; type B (severe neonatal form), in which affected infants have hepatomegaly, pyramidal tract signs, and abnormal movement and die within the first three months of life; and type C (intermittent/benign form), in which affected individuals have normal or mildly delayed neurologic development and episodic metabolic acidosis.

Diagnosis Testing

The diagnosis of PC deficiency rests on analysis of amino acids and organic acids and detection of deficiency of PC enzyme activity measured in fibroblasts. Molecular genetic testing of PC, the only gene known to be associated with PC deficiency, is available.

Genetic Counseling

PC deficiency is inherited in an autosomal recessive manner. De novo somatic mutations have been reported. If both parents are carriers, sibs of an individual with PC deficiency have a 25% chance of inheriting both mutations and being affected, a 50% chance of inheriting one mutated gene and being carriers, and a 25% chance of inheriting both normal genes and not being carriers. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk is possible by molecular genetic testing if both disease-causing alleles have been identified in an affected family member.

References

PMID: 20301764

NHGRI GWAS Catalog

Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.

Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P11498	P00505	GOT2	HPRD	PubMed
P11498	P40926	MDH2	HPRD	PubMed
BioGRID:111124	BioGRID:107435	CDH2	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:109067	GOT1	BioGRID	PubMed	Reconstituted Complex
BioGRID:111124	BioGRID:109659	IFIT1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111124	BioGRID:109821	ILF2	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:109822	ILF3	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:110356	MDH2	BioGRID	PubMed	Reconstituted Complex
BioGRID:111124	BioGRID:110622	MTHFD1	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:110748	NACA	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:110929	NPM1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111124	BioGRID:114775	PPT2	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:125187	PRKCDBP	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:112103	RPS3A	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:113135	TUFM	BioGRID	PubMed	Co-fractionation
BioGRID:111124	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111124	BioGRID:113182	UBE2N	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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Alanine and aspartate metabolism, organism-specific biosystem (from WikiPathways)
Alanine and aspartate metabolism, organism-specific biosystem
Alanine and aspartate metabolism
Biosynthesis of amino acids, organism-specific biosystem (from KEGG)
Biosynthesis of amino acids, organism-specific biosystem
Biosynthesis of amino acids
Biosynthesis of amino acids, conserved biosystem (from KEGG)
Biosynthesis of amino acids, conserved biosystem
Biosynthesis of amino acids
Citrate cycle (TCA cycle), organism-specific biosystem (from KEGG)
Citrate cycle (TCA cycle), organism-specific biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Citrate cycle (TCA cycle), conserved biosystem (from KEGG)
Citrate cycle (TCA cycle), conserved biosystemThe citrate cycle (TCA cycle, Krebs cycle) is an important aerobic pathway for the final steps of the oxidation of carbohydrates and fatty acids. The cycle starts with acetyl-CoA, the activated form ...
Fatty Acid Biosynthesis, organism-specific biosystem (from WikiPathways)
Fatty Acid Biosynthesis, organism-specific biosystem
Fatty Acid Biosynthesis
Gluconeogenesis, organism-specific biosystem (from REACTOME)
Gluconeogenesis, organism-specific biosystemThe reactions of gluconeogenesis convert mitochondrial pyruvate to cytosolic glucose 6-phosphate which in turn can be hydrolyzed to glucose and exported from the cell. Gluconeogenesis is confined to ...
Glucose metabolism, organism-specific biosystem (from REACTOME)
Glucose metabolism, organism-specific biosystemGlucose is the major form in which dietary sugars are made available to cells of the human body. Its breakdown is a major source of energy for all cells, and is essential for the brain and red blood ...
Glycolysis and Gluconeogenesis, organism-specific biosystem (from WikiPathways)
Glycolysis and Gluconeogenesis, organism-specific biosystem
Glycolysis and Gluconeogenesis
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
Pyruvate metabolism, organism-specific biosystem (from KEGG)
Pyruvate metabolism, organism-specific biosystem
Pyruvate metabolism
Pyruvate metabolism, conserved biosystem (from KEGG)
Pyruvate metabolism, conserved biosystem
Pyruvate metabolism
gluconeogenesis, organism-specific biosystem (from BIOCYC)
gluconeogenesis, organism-specific biosystem
gluconeogenesis

General gene information

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Markers

D1S1178 (e-PCR)
- UniSTS:66084

PC (e-PCR)
- UniSTS:49448

SHGC-30028 (e-PCR)
- UniSTS:48451

G07232 (e-PCR)
- UniSTS:15435

GDB:197884 (e-PCR)
- UniSTS:155987

D11S2683 (e-PCR)
- UniSTS:151908

STS-U30889 (e-PCR)
- UniSTS:54126

RH98812 (e-PCR)
- UniSTS:83853

RH92701 (e-PCR)
- UniSTS:87192

SHGC-144979 (e-PCR)
- UniSTS:172496

Genotypes

See PC SNP Geneview Report
See PC SNP Genotype Report
See PC SNP Variation Viewer Report

Homology

Homologs of the PC gene: The PC gene is conserved in Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, and N.crassa.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
DNA binding	IEA Inferred from Electronic Annotation more info
biotin binding	IEA Inferred from Electronic Annotation more info
biotin carboxylase activity	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
pyruvate carboxylase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
carbohydrate metabolic process	TAS Traceable Author Statement more info
gluconeogenesis	IEA Inferred from Electronic Annotation more info
gluconeogenesis	TAS Traceable Author Statement more info
glucose metabolic process	TAS Traceable Author Statement more info
lipid metabolic process	IEA Inferred from Electronic Annotation more info
oxaloacetate metabolic process	IEA Inferred from Electronic Annotation more info
pyruvate metabolic process	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
mitochondrial inner membrane	IEA Inferred from Electronic Annotation more info
mitochondrial matrix	TAS Traceable Author Statement more info
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: pyruvate carboxylase, mitochondrial

Names: pyruvate carboxylase, mitochondrial; pyruvic carboxylase

NP_000911.2

EC 6.4.1.1

NP_001035806.1

EC 6.4.1.1

NP_071504.2

EC 6.4.1.1

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

NG_008319.1 RefSeqGene

Range

5001..114851

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000920.3 → NP_000911.2 pyruvate carboxylase, mitochondrial precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) results from the use of a more distal promoter. Transcript variants 1-3 encode the same protein.

Source sequence(s)

BC011617, DA542083

Consensus CDS

CCDS8152.1

UniProtKB/Swiss-Prot

P11498

Related

ENSP00000377530, OTTHUMP00000235156, ENST00000393958, OTTHUMT00000393115

Conserved Domains (6) summary

cd06850
Location:1111 – 1177
Blast Score: 240

biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...

cd07937
Location:565 – 848
Blast Score: 1085

DRE_TIM_PC_TC_5S; Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain

PRK12999
Location:33 – 1178
Blast Score: 4555

PRK12999; pyruvate carboxylase; Reviewed

smart00878
Location:375 – 482
Blast Score: 423

Biotin_carb_C; Biotin carboxylase C-terminal domain

pfam00289
Location:37 – 145
Blast Score: 448

CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain

cl03087
Location:172 – 329
Blast Score: 142

ATP-grasp_4; ATP-grasp domain
NM_001040716.1 → NP_001035806.1 pyruvate carboxylase, mitochondrial precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) also results from the use of a more distal promoter, however, it contains an additional 5' non-coding exon, hence has a longer 5' UTR compared to transcript variant 1. Transcript variants 1-3 encode the same protein.

Source sequence(s)

BC011617, CN267865, DA542083

Consensus CDS

CCDS8152.1

UniProtKB/Swiss-Prot

P11498

Related

ENSP00000377532, ENST00000393960

Conserved Domains (6) summary

cd06850
Location:1111 – 1177
Blast Score: 240

biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...

cd07937
Location:565 – 848
Blast Score: 1085

DRE_TIM_PC_TC_5S; Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain

PRK12999
Location:33 – 1178
Blast Score: 4555

PRK12999; pyruvate carboxylase; Reviewed

smart00878
Location:375 – 482
Blast Score: 423

Biotin_carb_C; Biotin carboxylase C-terminal domain

pfam00289
Location:37 – 145
Blast Score: 448

CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain

cl03087
Location:172 – 329
Blast Score: 142

ATP-grasp_4; ATP-grasp domain
NM_022172.2 → NP_071504.2 pyruvate carboxylase, mitochondrial precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate 5' non-coding exon resulting from the use of a more proximal promoter, hence has a distinct 5' UTR compared to transcript variant 1. Transcript variants 1-3 encode the same protein.

Source sequence(s)

S72370, U30891

Consensus CDS

CCDS8152.1

UniProtKB/Swiss-Prot

P11498

Related

ENSP00000377527, OTTHUMP00000235155, ENST00000393955, OTTHUMT00000393114

Conserved Domains (6) summary

cd06850
Location:1111 – 1177
Blast Score: 240

biotinyl_domain; The biotinyl-domain or biotin carboxyl carrier protein (BCCP) domain is present in all biotin-dependent enzymes, such as acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, geranyl-CoA carboxylase, ...

cd07937
Location:565 – 848
Blast Score: 1085

DRE_TIM_PC_TC_5S; Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain

PRK12999
Location:33 – 1178
Blast Score: 4555

PRK12999; pyruvate carboxylase; Reviewed

smart00878
Location:375 – 482
Blast Score: 423

Biotin_carb_C; Biotin carboxylase C-terminal domain

pfam00289
Location:37 – 145
Blast Score: 448

CPSase_L_chain; Carbamoyl-phosphate synthase L chain, N-terminal domain

cl03087
Location:172 – 329
Blast Score: 142

ATP-grasp_4; ATP-grasp domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p10 Primary Assembly

Range

66615997..66725847, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

62944043..63053644, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018922.1 Alternate CHM1_1.0

Range

66535884..66644092, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01024056.1 (5804..14765)	None
genomic	ABBA01024057.1	None
genomic	ABBA01024058.1	None
genomic	ABBA01024059.1	None
genomic	ABBA01024060.1	None
genomic	AMYH01003736.1 (120130..175354)	None
genomic	AMYH01003737.1	None
genomic	AP000485.5 (122251..129626)	None
genomic	AP003176.2	None
genomic	CH471076.1	EAW74568.1
		EAW74569.1
		EAW74570.1
		EAW74571.1
		EAW74572.1
genomic	HB872407.1	CBF60260.1
genomic	HB873667.1	CBF61085.1
genomic	HB875538.1	CBF62141.1
genomic	HB880048.1	CBF64322.1
genomic	HB888783.1	CBF68536.1
genomic	HB921592.1	CBF95786.1
genomic	HC929816.1	CBU85504.1
genomic	HC931076.1	CBU86113.1
genomic	HC932947.1	CBU87017.1
genomic	HC937457.1	CBU89198.1
genomic	HC946192.1	CBU93410.1
genomic	HC979001.1	CBV09306.1
mRNA	AK297705.1	BAG60062.1
mRNA	BC011617.2	AAH11617.1
mRNA	CN267865.1	None
mRNA	DA542083.1	None
mRNA	K02282.1	AAA60033.1
mRNA	M26122.1	AAA36423.1
mRNA	S72370.1	AAB31500.1
mRNA	U04641.1	AAA99537.1
mRNA	U30889.1	None
mRNA	U30890.1	None
mRNA	U30891.1	AAA82937.1