PC

Protein identityUniProt · HPA

UniProt accession

P11498

Gene

PC

Ensembl

ENSG00000173599

Chromosome

11

Canonical length

1178 aa

Protein class

Citric acid cycle related proteins, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1178 residues, UniProt reviewed canonical sequence.

>P11498|PC
     1  MLKFRTVHGG LRLLGIRRTS TAPAASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG
    61  IRTVAIYSEQ DTGQMHRQKA DEAYLIGRGL APVQAYLHIP DIIKVAKENN VDAVHPGYGF
   121  LSERADFAQA CQDAGVRFIG PSPEVVRKMG DKVEARAIAI AAGVPVVPGT DAPITSLHEA
   181  HEFSNTYGFP IIFKAAYGGG GRGMRVVHSY EELEENYTRA YSEALAAFGN GALFVEKFIE
   241  KPRHIEVQIL GDQYGNILHL YERDCSIQRR HQKVVEIAPA AHLDPQLRTR LTSDSVKLAK
   301  QVGYENAGTV EFLVDRHGKH YFIEVNSRLQ VEHTVTEEIT DVDLVHAQIH VAEGRSLPDL
   361  GLRQENIRIN GCAIQCRVTT EDPARSFQPD TGRIEVFRSG EGMGIRLDNA SAFQGAVISP
   421  HYDSLLVKVI AHGKDHPTAA TKMSRALAEF RVRGVKTNIA FLQNVLNNQQ FLAGTVDTQF
   481  IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVKA SPSPTDPVVP AVPIGPPPAG
   541  FRDILLREGP EGFARAVRNH PGLLLMDTTF RDAHQSLLAT RVRTHDLKKI APYVAHNFSK
   601  LFSMENWGGA TFDVAMRFLY ECPWRRLQEL RELIPNIPFQ MLLRGANAVG YTNYPDNVVF
   661  KFCEVAKENG MDVFRVFDSL NYLPNMLLGM EAAGSAGGVV EAAISYTGDV ADPSRTKYSL
   721  QYYMGLAEEL VRAGTHILCI KDMAGLLKPT ACTMLVSSLR DRFPDLPLHI HTHDTSGAGV
   781  AAMLACAQAG ADVVDVAADS MSGMTSQPSM GALVACTRGT PLDTEVPMER VFDYSEYWEG
   841  ARGLYAAFDC TATMKSGNSD VYENEIPGGQ YTNLHFQAHS MGLGSKFKEV KKAYVEANQM
   901  LGDLIKVTPS SKIVGDLAQF MVQNGLSRAE AEAQAEELSF PRSVVEFLQG YIGVPHGGFP
   961  EPFRSKVLKD LPRVEGRPGA SLPPLDLQAL EKELVDRHGE EVTPEDVLSA AMYPDVFAHF
  1021  KDFTATFGPL DSLNTRLFLQ GPKIAEEFEV ELERGKTLHI KALAVSDLNR AGQRQVFFEL
  1081  NGQLRSILVK DTQAMKEMHF HPKALKDVKG QIGAPMPGKV IDIKVVAGAK VAKGQPLCVL
  1141  SAMKMETVVT SPMEGTVRKV HVTKDMTLEG DDLILEIE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PC can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

182 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PC.

Disease | AllUniProt

Conditions PC is implicated in, by any mechanism.

• Pyruvate carboxylase deficiency (PC deficiency) MIM:266150

Disease | GeneticClinVar

180 pathogenic / likely-pathogenic of 1,527 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Pyruvate carboxylase deficiency
• Congenital lactic acidosis
• Global developmental delay
• Thrombophilia due to protein C deficiency, autosomal dominant
• Thrombophilia due to protein C deficiency, autosomal recessive

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.44

gnomAD pLI

0.01

gnomAD missense Z

3.06

DepMap mean gene effect

-0.32

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• gluconeogenesis
• host-mediated activation of viral process
• lipid metabolic process
• NAD+ metabolic process
• NADP+ metabolic process
• negative regulation of gene expression
• viral release from host cell
• viral RNA genome packaging

Molecular functions

• ATP binding
• biotin binding
• identical protein binding
• metal ion binding
• pyruvate carboxylase activity

Cellular components

• cytoplasm
• cytosol
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Biotin/lipoyl attachment
• Pyruvate carboxyltransferase
• Biotin-binding site
• Carbamoyl phosphate synthase, ATP-binding domain
• Biotin carboxylase-like, N-terminal domain
• Biotin carboxylase, C-terminal
• Single hybrid motif
• Rudiment single hybrid motif
• ATP-grasp fold
• Biotin carboxylation domain
• Aldolase-type TIM barrel
• Pre-ATP-grasp domain superfamily
• Biotin carboxylase, N-terminal domain
• Biotin-requiring enzyme
• HMGL-like
• Biotin carboxylase C-terminal domain
• Carbamoyl-phosphate synthase L chain, ATP binding domain
• Carboxylase, conserved domain
• Pyruvate carboxylase
• Pyruvate carboxylase-like
• Conserved carboxylase domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Biotin
• Gluconeogenesis
• Ligase
• Lipid biosynthesis
• Lipid metabolism
• Manganese
• Metal-binding
• Mitochondrion
• Multifunctional enzyme
• Nucleotide-binding
• Phosphoprotein
• Pyruvate
• Transit peptide

InteractionsUniProt · HPA

Protein binding partners of PC in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• SIRT4