Human Gene PC (ENST00000393955.6) from GENCODE V44
  Description: Homo sapiens pyruvate carboxylase (PC), transcript variant 2, mRNA. (from RefSeq NM_022172)
RefSeq Summary (NM_022172): 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].
Gencode Transcript: ENST00000393955.6
Gencode Gene: ENSG00000173599.15
Transcript (Including UTRs)
   Position: hg38 chr11:66,848,513-66,907,901 Size: 59,389 Total Exon Count: 21 Strand: -
Coding Region
   Position: hg38 chr11:66,848,899-66,872,159 Size: 23,261 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr11:66,848,513-66,907,901)mRNA (may differ from genome)Protein (1178 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGImyGene2
neXtProtOMIMPubMedReactomeUniProtKBWikipedia
BioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PYC_HUMAN
DESCRIPTION: RecName: Full=Pyruvate carboxylase, mitochondrial; EC=6.4.1.1; AltName: Full=Pyruvic carboxylase; Short=PCB; Flags: Precursor;
FUNCTION: Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate.
CATALYTIC ACTIVITY: ATP + pyruvate + HCO(3)(-) = ADP + phosphate + oxaloacetate.
COFACTOR: Biotin.
COFACTOR: Binds 1 manganese ion per subunit.
PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
SUBUNIT: Homotetramer.
SUBCELLULAR LOCATION: Mitochondrion matrix.
DISEASE: Defects in PC are the cause of pyruvate carboxylase deficiency (PC deficiency) [MIM:266150]. PC deficiency leads to lactic acidosis, mental retardation and death. It occurs in three forms: mild or type A, severe neonatal or type B, and a very mild lacticacidemia.
SIMILARITY: Contains 1 ATP-grasp domain.
SIMILARITY: Contains 1 biotin carboxylation domain.
SIMILARITY: Contains 1 biotinyl-binding domain.
SIMILARITY: Contains 1 carboxyltransferase domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PC";
WEB RESOURCE: Name=Wikipedia; Note=Pyruvate carboxylase entry; URL="http://en.wikipedia.org/wiki/Pyruvate_carboxylase";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PC
Diseases sorted by gene-association score: pyruvate carboxylase deficiency* (1703), radial neuropathy (16), holocarboxylase synthetase deficiency (14), lactic acidosis (14), multiple carboxylase deficiency (12), biotin deficiency (12), acute porphyria (11), pyruvate dehydrogenase e1-alpha deficiency (10), citrullinemia (9), hyperlysinemia (8), reye syndrome (8), monocarboxylate transporter 1 deficiency (6), methylmalonic acidemia (6), encephalomalacia (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 72.06 RPKM in Liver
Total median expression: 534.29 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -30.1081-0.372 Picture PostScript Text
3' UTR -159.50386-0.413 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR013785 - Aldolase_TIM
IPR011761 - ATP-grasp
IPR013815 - ATP_grasp_subdomain_1
IPR013816 - ATP_grasp_subdomain_2
IPR001882 - Biotin_BS
IPR011764 - Biotin_carboxylation_dom
IPR005482 - Biotin_COase_C
IPR000089 - Biotin_lipoyl
IPR005481 - CarbamoylP_synth_lsu_N
IPR003379 - Carboxylase_cons_dom
IPR005479 - CbamoylP_synth_lsu-like_ATP-bd
IPR016185 - PreATP-grasp_fold
IPR000891 - PYR_CT
IPR005930 - Pyruv_COase
IPR011054 - Rudment_hybrid_motif
IPR011053 - Single_hybrid_motif

Pfam Domains:
PF02785 - Biotin carboxylase C-terminal domain
PF00364 - Biotin-requiring enzyme
PF00289 - Biotin carboxylase, N-terminal domain
PF02786 - Carbamoyl-phosphate synthase L chain, ATP binding domain
PF00682 - HMGL-like
PF02436 - Conserved carboxylase domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3BG3 - X-ray MuPIT 3BG9 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P11498
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003824 catalytic activity
GO:0004736 pyruvate carboxylase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0009374 biotin binding
GO:0016874 ligase activity
GO:0042802 identical protein binding
GO:0046872 metal ion binding

Biological Process:
GO:0006090 pyruvate metabolic process
GO:0006094 gluconeogenesis
GO:0006629 lipid metabolic process
GO:0006768 biotin metabolic process
GO:0008152 metabolic process
GO:0010629 negative regulation of gene expression
GO:0019074 viral RNA genome packaging
GO:0044791 positive regulation by host of viral release from host cell
GO:0044794 positive regulation by host of viral process

Cellular Component:
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005759 mitochondrial matrix
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  S72370 - pyruvate carboxylase [human, kidney, mRNA, 4017 nt].
U04641 - Human pyruvate carboxylase (PC) mRNA, complete cds.
BC011617 - Homo sapiens pyruvate carboxylase, mRNA (cDNA clone MGC:10528 IMAGE:3946441), complete cds.
U30891 - Human pyruvate carboxylase precursor, mRNA, nuclear gene encoding mitochondrial protein, complete cds.
JD470487 - Sequence 451511 from Patent EP1572962.
JD398387 - Sequence 379411 from Patent EP1572962.
JD094246 - Sequence 75270 from Patent EP1572962.
JD516254 - Sequence 497278 from Patent EP1572962.
JD375769 - Sequence 356793 from Patent EP1572962.
JD120959 - Sequence 101983 from Patent EP1572962.
JD190665 - Sequence 171689 from Patent EP1572962.
JD448143 - Sequence 429167 from Patent EP1572962.
K02282 - Human pyruvate carboxylase gene (pcb), 3' end.
M26122 - Human pyruvate carboxylase (PCC) mRNA, 3' end.
KJ891753 - Synthetic construct Homo sapiens clone ccsbBroadEn_01147 PC gene, encodes complete protein.
KR710310 - Synthetic construct Homo sapiens clone CCSBHm_00011442 PC (PC) mRNA, encodes complete protein.
KR710311 - Synthetic construct Homo sapiens clone CCSBHm_00011451 PC (PC) mRNA, encodes complete protein.
KR710312 - Synthetic construct Homo sapiens clone CCSBHm_00011452 PC (PC) mRNA, encodes complete protein.
AB527412 - Synthetic construct DNA, clone: pF1KB3701, Homo sapiens PC gene for pyruvate carboxylase, without stop codon, in Flexi system.
AK297705 - Homo sapiens cDNA FLJ60715 complete cds, highly similar to Pyruvate carboxylase, mitochondrial precursor (EC 6.4.1.1).
CU679988 - Synthetic construct Homo sapiens gateway clone IMAGE:100023457 5' read PC mRNA.
U30890 - Human pyruvate carboxylase mRNA, alternative 5' untranslated region.
JD497405 - Sequence 478429 from Patent EP1572962.
JD459917 - Sequence 440941 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00020 - Citrate cycle (TCA cycle)
hsa00620 - Pyruvate metabolism
hsa01100 - Metabolic pathways

Reactome (by CSHL, EBI, and GO)

Protein P11498 (Reactome details) participates in the following event(s):

R-HSA-2993802 HLCS biotinylates PC:Mn2+
R-HSA-70501 Pyruvate + CO2 + ATP => ADP + Orthophosphate + Oxaloacetate
R-HSA-196780 Biotin transport and metabolism
R-HSA-3371599 Defective HLCS causes multiple carboxylase deficiency
R-HSA-70263 Gluconeogenesis
R-HSA-196849 Metabolism of water-soluble vitamins and cofactors
R-HSA-3323169 Defects in biotin (Btn) metabolism
R-HSA-70326 Glucose metabolism
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-3296482 Defects in vitamin and cofactor metabolism
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1430728 Metabolism
R-HSA-5668914 Diseases of metabolism
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000393955.1, ENST00000393955.2, ENST00000393955.3, ENST00000393955.4, ENST00000393955.5, NM_022172, P11498, PYC_HUMAN, Q16705, uc001ojn.1, uc001ojn.2
UCSC ID: ENST00000393955.6
RefSeq Accession: NM_022172
Protein: P11498 (aka PYC_HUMAN)
CCDS: CCDS8152.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene PC:
pdc (Pyruvate Carboxylase Deficiency)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.