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    PC pyruvate carboxylase [ Homo sapiens (human) ]

    Gene ID: 5091, updated on 3-Nov-2024

    Summary

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    Official Symbol
    PCprovided by HGNC
    Official Full Name
    pyruvate carboxylaseprovided by HGNC
    Primary source
    HGNC:HGNC:8636
    See related
    Ensembl:ENSG00000173599 MIM:608786; AllianceGenome:HGNC:8636
    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]
    Expression
    Biased expression in fat (RPKM 30.0), liver (RPKM 19.3) and 13 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    Location:
    11q13.2
    Exon count:
    31
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (66848420..66958383, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (66844694..66952886, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (66615891..66725854, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene TOP6B like initiator of meiotic double strand breaks Neighboring gene ferritin light chain pseudogene 6 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66580049-66580832 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:66609109-66609235 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3603 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66610783-66611489 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66617715-66618294 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66618295-66618873 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3605 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3606 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5058 Neighboring gene Ras converting CAAX endopeptidase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66644024-66644524 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66644525-66645025 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66645752-66646490 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66649447-66650184 Neighboring gene leucine rich repeat and fibronectin type III domain containing 4 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66650185-66650922 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5059 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66672605-66673252 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5060 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66688620-66689560 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:66690541-66691041 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:66691815-66692466 Neighboring gene RNA, U7 small nuclear 23 pseudogene Neighboring gene microRNA 3163 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5061 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3607 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5062 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3608 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:66743456-66743959 Neighboring gene Sharpr-MPRA regulatory region 11253 Neighboring gene chromosome 11 open reading frame 86 Neighboring gene uncharacterized LOC124902849

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Breast Cancer-Derived Lung Metastases Show Increased Pyruvate Carboxylase-Dependent Anaplerosis. Christen S, et al. Cell Rep, 2016 Oct 11. PMID 27732858
    2. A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation. Schiff M, et al. Mol Genet Metab, 2006 Feb. PMID 16325442
    3. Expression and characterization of a human pyruvate carboxylase variant by retroviral gene transfer. Carbone MA, et al. Biochem J, 2003 Feb 15. PMID 12437512, Free PMC Article
    4. The ubiquitous expression of pyruvate carboxylase among human prostate tumors. Gondas E, et al. Bratisl Lek Listy, 2022. PMID 35907054
    5. Immunohistochemical localization of pyruvate carboxylase and carbamyl-phosphate synthetase I in normal and neoplastic human pancreatic tissues. Sato T, et al. Pancreas, 2002 Aug. PMID 12142734

    See all (157) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.
      Title: Leat-associated seizures the possible role of EAAT2, pyruvate carboxylase and glutamine synthetase.
    2. In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency.
      Title: In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency.
    3. The ubiquitous expression of pyruvate carboxylase among human prostate tumors.
      Title: The ubiquitous expression of pyruvate carboxylase among human prostate tumors.
    4. Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis.
      Title: Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis.
    5. Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment.
      Title: Fibroblast pyruvate carboxylase is required for collagen production in the tumour microenvironment.
    6. Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes.
      Title: Pyruvate carboxylase supports basal ATP-linked respiration in human pluripotent stem cell-derived brown adipocytes.
    7. Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.
      Title: Rethinking the Citric Acid Cycle: Connecting Pyruvate Carboxylase and Citrate Synthase to the Flow of Energy and Material.
    8. Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer.
      Title: Integrated analysis of transcriptomic and metabolomic data demonstrates the significant role of pyruvate carboxylase in the progression of ovarian cancer.
    9. Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells.
      Title: Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells.
    10. Overexpression of Pyruvate Carboxylase Is Correlated With Colorectal Cancer Progression and Supports Growth of Invasive Colon Cancer HT-29 Cell Line.
      Title: Overexpression of Pyruvate Carboxylase Is Correlated With Colorectal Cancer Progression and Supports Growth of Invasive Colon Cancer HT-29 Cell Line.
    Submit: New GeneRIF Correction See all GeneRIFs (28)

    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
    Pyruvate carboxylase deficiency
    MedGen: C0034341 OMIM: 266150 GeneReviews: Pyruvate Carboxylase Deficiency
    		Compare labs

    EBI GWAS Catalog

    Description
    Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
    EBI GWAS Catalog
    Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables biotin binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables pyruvate carboxylase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables pyruvate carboxylase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables pyruvate carboxylase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NADH metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in NADP metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in gluconeogenesis IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in gluconeogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gluconeogenesis TAS
    Traceable Author Statement
    more info
    		  
    involved_in lipid metabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation by host of viral process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in pyruvate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pyruvate metabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in viral RNA genome packaging IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in viral release from host cell IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    pyruvate carboxylase, mitochondrial
    Names
    pyruvic carboxylase
    NP_000911.2
    NP_001035806.1
    NP_071504.2
    XP_005274088.1
    XP_005274089.1
    XP_006718641.1
    XP_006718642.1
    XP_011543388.1
    XP_011543389.1
    XP_016873357.1
    XP_016873358.1
    XP_016873359.1
    XP_016873360.1
    XP_016873361.1
    XP_047283014.1
    XP_054224998.1
    XP_054224999.1
    XP_054225000.1
    XP_054225001.1
    XP_054225002.1
    XP_054225003.1
    XP_054225004.1
    XP_054225005.1
    XP_054225006.1
    XP_054225007.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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

    1. NG_008319.1 RefSeqGene

      Range
      4994..114957
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000920.4 → NP_000911.2  pyruvate carboxylase, mitochondrial precursor

      See identical proteins and their annotated locations for NP_000911.2

      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)
      AP000485, AP003176, BC011617, DA542083
      Consensus CDS
      CCDS8152.1
      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000377530.2, ENST00000393958.7
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    2. NM_001040716.2 → NP_001035806.1  pyruvate carboxylase, mitochondrial precursor

      See identical proteins and their annotated locations for NP_001035806.1

      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)
      AP000485, AP003176, BC011617, CN267865, DA542083
      Consensus CDS
      CCDS8152.1
      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000377532.1, ENST00000393960.7
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    3. NM_022172.3 → NP_071504.2  pyruvate carboxylase, mitochondrial precursor

      See identical proteins and their annotated locations for NP_071504.2

      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)
      AP000485, AP003176, S72370, U30891
      Consensus CDS
      CCDS8152.1
      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000377527.2, ENST00000393955.6
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    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

    1. NC_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      66848420..66958383 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006718578.4 → XP_006718641.1  pyruvate carboxylase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_006718641.1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    2. XM_017017871.2 → XP_016873360.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000435905.2, ENST00000529047.6
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    3. XM_017017869.2 → XP_016873358.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    4. XM_017017870.2 → XP_016873359.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000498302.1, ENST00000652125.1
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    5. XM_017017868.2 → XP_016873357.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Related
      ENSP00000498406.1, ENST00000651036.1
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    6. XM_017017872.3 → XP_016873361.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    7. XM_011545086.3 → XP_011543388.1  pyruvate carboxylase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_011543388.1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    8. XM_005274031.5 → XP_005274088.1  pyruvate carboxylase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_005274088.1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    9. XM_005274032.5 → XP_005274089.1  pyruvate carboxylase, mitochondrial isoform X1

      See identical proteins and their annotated locations for XP_005274089.1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705
      Conserved Domains (1) summary
      PRK12999
      Location:33 → 1178
      PRK12999; pyruvate carboxylase; Reviewed

    10. XM_047427058.1 → XP_047283014.1  pyruvate carboxylase, mitochondrial isoform X3

    11. XM_006718579.4 → XP_006718642.1  pyruvate carboxylase, mitochondrial isoform X3

      Conserved Domains (4) summary
      cd06850
      Location:604 → 670
      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:58 → 341
      DRE_TIM_PC_TC_5S; Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain
      PRK09282
      Location:60 → 671
      PRK09282; pyruvate carboxylase subunit B; Validated
      pfam02436
      Location:354 → 553
      PYC_OADA; Conserved carboxylase domain

    12. XM_011545087.3 → XP_011543389.1  pyruvate carboxylase, mitochondrial isoform X2

      Conserved Domains (5) summary
      cd06850
      Location:679 → 745
      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:133 → 416
      DRE_TIM_PC_TC_5S; Pyruvate carboxylase and Transcarboxylase 5S, carboxyltransferase domain
      PRK09282
      Location:135 → 746
      PRK09282; pyruvate carboxylase subunit B; Validated
      pfam02436
      Location:429 → 628
      PYC_OADA; Conserved carboxylase domain
      cl08365
      Location:24 → 50
      Biotin_carb_C; Biotin carboxylase C-terminal domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      66844694..66952886 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054369027.1 → XP_054225002.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    2. XM_054369025.1 → XP_054225000.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    3. XM_054369029.1 → XP_054225004.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    4. XM_054369023.1 → XP_054224998.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    5. XM_054369024.1 → XP_054224999.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    6. XM_054369028.1 → XP_054225003.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    7. XM_054369026.1 → XP_054225001.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    8. XM_054369030.1 → XP_054225005.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    9. XM_054369031.1 → XP_054225006.1  pyruvate carboxylase, mitochondrial isoform X1

      UniProtKB/Swiss-Prot
      B4DN00, P11498, Q16705

    10. XM_054369032.1 → XP_054225007.1  pyruvate carboxylase, mitochondrial isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P11498.2 GenPept UniProtKB/Swiss-Prot:P11498

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