LOCUS       NM_001040716            4305 bp    mRNA    linear   PRI 10-OCT-2024
DEFINITION  Homo sapiens pyruvate carboxylase (PC), transcript variant 3, mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_001040716
VERSION     NM_001040716.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4305)
  AUTHORS   Buccoliero,A.M., Caporalini,C., Moscardi,S., Cetica,V., Mei,D.,
            Conti,V., Nozzoli,F., Bonaudo,C., Battista,F., Giordano,F.,
            Mura,R., Spacca,B., Mussa,F., D'Onofrio,V., Guerrini,R.,
            Genitori,L. and Scagnet,M.
  TITLE     Leat-associated seizures the possible role of EAAT2, pyruvate
            carboxylase and glutamine synthetase
  JOURNAL   Epilepsy Res 199, 107258 (2024)
   PUBMED   38086219
  REMARK    GeneRIF: Leat-associated seizures the possible role of EAAT2,
            pyruvate carboxylase and glutamine synthetase.
REFERENCE   2  (bases 1 to 4305)
  AUTHORS   Maryami,F., Rismani,E., Davoudi-Dehaghani,E., Khalesi,N.,
            Talebi,S., Mahdian,R. and Zeinali,S.
  TITLE     In silico Analysis of Two Novel Variants in the Pyruvate
            Carboxylase (PC) Gene Associated with the Severe Form of PC
            Deficiency
  JOURNAL   Iran Biomed J 27 (5), 307-319 (2023)
   PUBMED   37873728
  REMARK    GeneRIF: In silico Analysis of Two Novel Variants in the Pyruvate
            Carboxylase (PC) Gene Associated with the Severe Form of PC
            Deficiency.
REFERENCE   3  (bases 1 to 4305)
  AUTHORS   Gondas,E., Hives,M., Kliment,J., Kmetova Sivonova,M., Dobrota,D.
            and Murin,R.
  TITLE     The ubiquitous expression of pyruvate carboxylase among human
            prostate tumors
  JOURNAL   Bratisl Lek Listy 123 (7), 487-490 (2022)
   PUBMED   35907054
  REMARK    GeneRIF: The ubiquitous expression of pyruvate carboxylase among
            human prostate tumors.
REFERENCE   4  (bases 1 to 4305)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   5  (bases 1 to 4305)
  AUTHORS   Schworer,S., Pavlova,N.N., Cimino,F.V., King,B., Cai,X.,
            Sizemore,G.M. and Thompson,C.B.
  TITLE     Fibroblast pyruvate carboxylase is required for collagen production
            in the tumour microenvironment
  JOURNAL   Nat Metab 3 (11), 1484-1499 (2021)
   PUBMED   34764457
  REMARK    GeneRIF: Fibroblast pyruvate carboxylase is required for collagen
            production in the tumour microenvironment.
REFERENCE   6  (bases 1 to 4305)
  AUTHORS   Walker,M.E., Baker,E., Wallace,J.C. and Sutherland,G.R.
  TITLE     Assignment of the human pyruvate carboxylase gene (PC) to 11q13.4
            by fluorescence in situ hybridisation
  JOURNAL   Cytogenet Cell Genet 69 (3-4), 187-189 (1995)
   PUBMED   7698008
REFERENCE   7  (bases 1 to 4305)
  AUTHORS   Duque Lasio,M.L., Lehman,A.N., Ahmad,A. and Bedoyan,J.K.
  TITLE     Pyruvate Carboxylase Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20301764
REFERENCE   8  (bases 1 to 4305)
  AUTHORS   Peng,L., Hertz,L., Huang,R., Sonnewald,U., Petersen,S.B.,
            Westergaard,N., Larsson,O. and Schousboe,A.
  TITLE     Utilization of glutamine and of TCA cycle constituents as
            precursors for transmitter glutamate and GABA
  JOURNAL   Dev Neurosci 15 (3-5), 367-377 (1993)
   PUBMED   7805591
  REMARK    Review article
REFERENCE   9  (bases 1 to 4305)
  AUTHORS   Lamhonwah,A.M., Quan,F. and Gravel,R.A.
  TITLE     Sequence homology around the biotin-binding site of human
            propionyl-CoA carboxylase and pyruvate carboxylase
  JOURNAL   Arch Biochem Biophys 254 (2), 631-636 (1987)
   PUBMED   3555348
REFERENCE   10 (bases 1 to 4305)
  AUTHORS   Freytag,S.O. and Collier,K.J.
  TITLE     Molecular cloning of a cDNA for human pyruvate carboxylase.
            Structural relationship to other biotin-containing carboxylases and
            regulation of mRNA content in differentiating preadipocytes
  JOURNAL   J Biol Chem 259 (20), 12831-12837 (1984)
   PUBMED   6548474
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP003176.2, DA542083.1,
            CN267865.1, BC011617.2 and AP000485.5.
            This sequence is a reference standard in the RefSeqGene project.
            
            On May 17, 2019 this sequence version replaced NM_001040716.1.
            
            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].
            
            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.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803612.145698.1,
                                           SRR1803617.27410.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000393960.7/
                                                  ENSP00000377532.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-7                 AP003176.2         102477-102483       c
            8-13                DA542083.1         1-6
            14-709              CN267865.1         12-707
            710-4199            BC011617.2         504-3993
            4200-4305           AP000485.5         122146-122251       c
FEATURES             Location/Qualifiers
     source          1..4305
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q13.2"
     gene            1..4305
                     /gene="PC"
                     /gene_synonym="PCB"
                     /note="pyruvate carboxylase"
                     /db_xref="GeneID:5091"
                     /db_xref="HGNC:HGNC:8636"
                     /db_xref="MIM:608786"
     exon            1..62
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            63..250
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            251..289
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     CDS             290..3826
                     /gene="PC"
                     /gene_synonym="PCB"
                     /EC_number="6.4.1.1"
                     /note="pyruvate carboxylase, mitochondrial; pyruvic
                     carboxylase"
                     /codon_start=1
                     /product="pyruvate carboxylase, mitochondrial precursor"
                     /protein_id="NP_001035806.1"
                     /db_xref="CCDS:CCDS8152.1"
                     /db_xref="GeneID:5091"
                     /db_xref="HGNC:HGNC:8636"
                     /db_xref="MIM:608786"
                     /translation="MLKFRTVHGGLRLLGIRRTSTAPAASPNVRRLEYKPIKKVMVAN
                     RGEIAIRVFRACTELGIRTVAIYSEQDTGQMHRQKADEAYLIGRGLAPVQAYLHIPDI
                     IKVAKENNVDAVHPGYGFLSERADFAQACQDAGVRFIGPSPEVVRKMGDKVEARAIAI
                     AAGVPVVPGTDAPITSLHEAHEFSNTYGFPIIFKAAYGGGGRGMRVVHSYEELEENYT
                     RAYSEALAAFGNGALFVEKFIEKPRHIEVQILGDQYGNILHLYERDCSIQRRHQKVVE
                     IAPAAHLDPQLRTRLTSDSVKLAKQVGYENAGTVEFLVDRHGKHYFIEVNSRLQVEHT
                     VTEEITDVDLVHAQIHVAEGRSLPDLGLRQENIRINGCAIQCRVTTEDPARSFQPDTG
                     RIEVFRSGEGMGIRLDNASAFQGAVISPHYDSLLVKVIAHGKDHPTAATKMSRALAEF
                     RVRGVKTNIAFLQNVLNNQQFLAGTVDTQFIDENPELFQLRPAQNRAQKLLHYLGHVM
                     VNGPTTPIPVKASPSPTDPVVPAVPIGPPPAGFRDILLREGPEGFARAVRNHPGLLLM
                     DTTFRDAHQSLLATRVRTHDLKKIAPYVAHNFSKLFSMENWGGATFDVAMRFLYECPW
                     RRLQELRELIPNIPFQMLLRGANAVGYTNYPDNVVFKFCEVAKENGMDVFRVFDSLNY
                     LPNMLLGMEAAGSAGGVVEAAISYTGDVADPSRTKYSLQYYMGLAEELVRAGTHILCI
                     KDMAGLLKPTACTMLVSSLRDRFPDLPLHIHTHDTSGAGVAAMLACAQAGADVVDVAA
                     DSMSGMTSQPSMGALVACTRGTPLDTEVPMERVFDYSEYWEGARGLYAAFDCTATMKS
                     GNSDVYENEIPGGQYTNLHFQAHSMGLGSKFKEVKKAYVEANQMLGDLIKVTPSSKIV
                     GDLAQFMVQNGLSRAEAEAQAEELSFPRSVVEFLQGYIGVPHGGFPEPFRSKVLKDLP
                     RVEGRPGASLPPLDLQALEKELVDRHGEEVTPEDVLSAAMYPDVFAHFKDFTATFGPL
                     DSLNTRLFLQGPKIAEEFEVELERGKTLHIKALAVSDLNRAGQRQVFFELNGQLRSIL
                     VKDTQAMKEMHFHPKALKDVKGQIGAPMPGKVIDIKVVAGAKVAKGQPLCVLSAMKME
                     TVVTSPMEGTVRKVHVTKDMTLEGDDLILEIE"
     exon            290..425
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            426..610
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            611..776
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            777..922
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            923..1040
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1041..1192
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1193..1311
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1312..1474
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1475..1657
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1658..1802
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1803..1892
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            1893..2114
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            2115..2271
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            2272..2512
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            2513..2762
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            2763..3007
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            3008..3187
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            3188..3436
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            3437..3577
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     exon            3578..4305
                     /gene="PC"
                     /gene_synonym="PCB"
                     /inference="alignment:Splign:2.1.0"
     regulatory      4178..4183
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PC"
                     /gene_synonym="PCB"
                     /note="hexamer: AATAAA"
     polyA_site      4200
                     /gene="PC"
                     /gene_synonym="PCB"
                     /note="major polyA site"
     polyA_site      4305
                     /gene="PC"
                     /gene_synonym="PCB"
ORIGIN      
        1 gttctctgtc agtggaggca gcagcggtag aggcggcggc gaggactggc gacggcgagg
       61 agctgccttc tagtctcacc tgtggacact ttgccaaagg agtcgggcct gacggtggaa
      121 gatgggaaat ggccaaaaga ataaaccatt tcctcttact taccgaatga aaagcttgct
      181 tcatcttggc gttcaagact ctctaatatg attccacctg ttgggctctt tcttccattt
      241 gcctccgcag atagtgtctg ccttctggag agctgaccaa acactaagga tgctgaagtt
      301 ccgaacagtc catgggggcc tgaggctcct gggaatccgc cgaacctcca ccgcccccgc
      361 tgcctcccca aatgtccggc gcctggagta taagcccatc aagaaagtca tggtggccaa
      421 cagaggtgag attgccatcc gtgtgttccg ggcctgcacg gagctgggca tccgcaccgt
      481 agccatctac tctgagcagg acacgggcca gatgcaccgg cagaaagcag atgaagccta
      541 tctcatcggc cgcggcctgg cccccgtgca ggcctacctg cacatcccag acatcatcaa
      601 ggtggccaag gagaacaacg tagatgcagt gcaccctggc tacgggttcc tctctgagcg
      661 agcggacttc gcccaggcct gccaggatgc aggggtccgg tttattgggc caagcccaga
      721 agtggtccgc aagatgggag acaaggtgga ggcccgggcc atcgccattg ctgcgggtgt
      781 tcccgttgtc cctggcacag atgcccccat cacgtccctg catgaggccc acgagttctc
      841 caacacctac ggcttcccca tcatcttcaa ggcggcctat gggggtggag ggcgtggcat
      901 gagggtggtg cacagctacg aggagctgga ggagaattac acccgggcct actcagaggc
      961 tctggccgcc tttgggaatg gggcgctgtt tgtggagaag ttcatcgaga agccacggca
     1021 catcgaggtg cagatcttgg gggaccagta tgggaacatc ctgcacctgt acgagcgaga
     1081 ctgctccatc cagcggcggc accagaaggt ggtcgagatt gcccccgccg cccacctgga
     1141 cccgcagctt cggactcggc tcaccagcga ctctgtgaaa ctcgctaaac aggtgggcta
     1201 cgagaacgca ggcaccgtgg agttcctggt ggacaggcac ggcaagcact acttcatcga
     1261 ggtcaactcc cgcctgcagg tggagcacac ggtcacagag gagatcaccg acgtagacct
     1321 ggtccatgct cagatccacg tggctgaggg caggagccta cccgacctgg gcctgcggca
     1381 ggagaacatc cgcatcaacg ggtgtgccat ccagtgccgg gtcaccaccg aggaccccgc
     1441 gcgcagcttc cagccggaca ccggccgcat tgaggtgttc cggagcggag agggcatggg
     1501 catccgcctg gataatgctt ccgccttcca aggagccgtc atctcgcccc actacgactc
     1561 cctgctggtc aaagtcattg cccacggcaa agaccacccc acggccgcca ccaagatgag
     1621 cagggccctt gcggagttcc gcgtccgagg tgtgaagacc aacatcgcct tcctgcagaa
     1681 tgtgctcaac aaccagcagt tcctggcagg cactgtggac acccagttca tcgacgagaa
     1741 cccagagctg ttccagctgc ggcctgcaca gaaccgggcc caaaagctgt tgcactacct
     1801 cggccatgtc atggtaaacg gtccaaccac cccgattccc gtcaaggcca gccccagccc
     1861 cacggacccc gttgtccctg cagtgcccat aggcccgccc ccggctggtt tcagagacat
     1921 cctgctgcga gaggggcctg agggctttgc tcgagctgtg cggaaccacc cggggctgct
     1981 gctgatggac acgaccttca gggacgccca ccagtcactg ctggccactc gtgtgcgcac
     2041 ccacgatctc aaaaagatcg ccccctatgt tgcccacaac ttcagcaagc tcttcagcat
     2101 ggagaactgg ggaggagcca cgtttgacgt cgccatgcgc ttcctgtatg agtgcccctg
     2161 gcggcggctg caggagctcc gggagctcat ccccaacatc cctttccaga tgctgctgcg
     2221 gggggccaat gctgtgggct acaccaacta cccagacaac gtggtcttca agttctgtga
     2281 agtggccaaa gagaatggca tggatgtctt ccgtgtgttt gactccctca actacttgcc
     2341 caacatgctg ctgggcatgg aggcggcagg aagtgccgga ggcgtggtgg aggctgccat
     2401 ctcatacacg ggcgacgtgg ccgaccccag ccgcaccaag tactcactgc agtactacat
     2461 gggcttggcc gaagagctgg tgcgagctgg cacccacatc ctgtgcatca aggacatggc
     2521 cgggctgctg aagcccacgg cctgcaccat gctggtcagc tccctccggg accgcttccc
     2581 cgacctccca ctgcacatcc acacccacga cacgtcaggg gcaggcgtgg cagccatgct
     2641 ggcctgtgcc caggctggag ctgatgtggt ggatgtggca gctgattcca tgtctgggat
     2701 gacttcacag cccagcatgg gggccctggt ggcctgtacc agagggactc ccctggacac
     2761 agaggtgccc atggagcgcg tgtttgacta cagtgagtac tgggaggggg ctcggggact
     2821 gtacgcggcc ttcgactgca cggccaccat gaagtctggc aactcggacg tgtatgaaaa
     2881 tgagatccca gggggccagt acaccaacct gcacttccag gcccacagca tggggcttgg
     2941 ctccaagttc aaggaggtca agaaggccta tgtggaggcc aaccagatgc tgggcgatct
     3001 catcaaggtg acgccctcct ccaagatcgt gggggacctg gcccagttta tggtgcagaa
     3061 tggattgagc cgggcagagg ccgaagctca ggcggaagag ctgtcctttc cccgctccgt
     3121 ggtggagttc ctgcagggct acatcggtgt cccccatggg gggttccccg aaccctttcg
     3181 ctctaaggta ctgaaggacc tgccaagggt ggaggggcgg cctggagcct ccctccctcc
     3241 cctggatctg caggcactgg agaaggagct ggtagaccgg catggggagg aggtgacgcc
     3301 ggaagatgtg ctctcagcag ctatgtaccc cgatgtgttt gcccacttca aggacttcac
     3361 tgccaccttt ggccccctgg atagcctgaa tactcgcctc ttcctgcagg gacccaagat
     3421 cgcagaggag tttgaggtgg agctggagcg gggcaagacg ctgcacatca aagccctggc
     3481 cgtgagcgac ctgaaccggg ccggccagag gcaggtcttc tttgagctca atgggcagct
     3541 gcggtccatc ttggtcaagg acacccaggc catgaaggag atgcacttcc accccaaggc
     3601 cctaaaggac gtgaagggcc agatcggggc gcccatgcct gggaaggtga tagacatcaa
     3661 agtggtggca ggggccaagg tggccaaggg ccagcccctg tgtgtgctca gtgccatgaa
     3721 gatggagact gtggtgacct cacccatgga gggtactgtc cgcaaggttc atgtgaccaa
     3781 ggacatgaca ctggaaggtg acgacctcat cctggagatc gagtgatctt gccccagacc
     3841 ggcagcctgg ccatccccaa gccttcaaca gaagctgtgc tgccacggca ggcccaggcc
     3901 agccagtgcc cgaggccagg aaggccgggc cgtggaggtc ctgtccacag ctggacagga
     3961 gagacaccgc ctgcggtggt tcattccttt cagccatcgt cctttcctcc ggcggacagc
     4021 tgcttacatg ttcatctctt gccaaataag ggtcccctcc tcactggaga ctacaagtgg
     4081 tgggtcaggt ggtcctagga cccaggggag gtttaggggt cctatctcct gggggaaggg
     4141 gagatctaag atgtcccagg tcctgggaag tttactcaat aaagctggct ttcccctgcc
     4201 ctccatgctg gatcctgtgc agcccccagc ctgcaccact cagcagtggg gggctgcctt
     4261 tcaagctccc catgggtggg caggtcagtt gtgtcgttct cctca
//
