PYC_HUMAN
ID PYC_HUMAN Reviewed; 1178 AA.
AC P11498; B4DN00; Q16705;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Pyruvate carboxylase, mitochondrial {ECO:0000305};
DE EC=6.4.1.1 {ECO:0000269|PubMed:9585002};
DE AltName: Full=Pyruvic carboxylase;
DE Short=PCB;
DE Flags: Precursor;
GN Name=PC {ECO:0000312|HGNC:HGNC:8636};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND BIOTINYLATION AT LYS-1144.
RC TISSUE=Kidney, and Liver;
RX PubMed=7918683; DOI=10.1016/0925-4439(94)90105-8;
RA Wexler I.D., Du Y., Lisgaris M.V., Mandal S.K., Freytag S.O., Yang B.-S.,
RA Liu T.-C., Kwon M., Patel M.S., Kerr D.S.;
RT "Primary amino acid sequence and structure of human pyruvate carboxylase.";
RL Biochim. Biophys. Acta 1227:46-52(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=8048912; DOI=10.1006/bbrc.1994.2029;
RA Mackay N., Rigat B., Douglas C., Chen H.S., Robinson B.H.;
RT "cDNA cloning of human kidney pyruvate carboxylase.";
RL Biochem. Biophys. Res. Commun. 202:1009-1014(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Kidney, and Liver;
RA Walker M.E., Jitrapakdee S., Val D.L., Wallace J.C.;
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1083-1178 (ISOFORM 1).
RX PubMed=3555348; DOI=10.1016/0003-9861(87)90146-9;
RA Lamhonwah A.-M., Quan F., Gravel R.A.;
RT "Sequence homology around the biotin-binding site of human propionyl-CoA
RT carboxylase and pyruvate carboxylase.";
RL Arch. Biochem. Biophys. 254:631-636(1987).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1135-1178 (ISOFORM 1), AND BIOTINYLATION AT
RP LYS-1144.
RX PubMed=6548474; DOI=10.1016/s0021-9258(18)90822-7;
RA Freytag S.O., Collier K.J.;
RT "Molecular cloning of a cDNA for human pyruvate carboxylase. Structural
RT relationship to other biotin-containing carboxylases and regulation of mRNA
RT content in differentiating preadipocytes.";
RL J. Biol. Chem. 259:12831-12837(1984).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1090, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP INTERACTION WITH SIRT4.
RX PubMed=23438705; DOI=10.1016/j.mito.2013.02.002;
RA Wirth M., Karaca S., Wenzel D., Ho L., Tishkoff D., Lombard D.B.,
RA Verdin E., Urlaub H., Jedrusik-Bode M., Fischle W.;
RT "Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals
RT interact with pyruvate carboxylase and other acetylated biotin-dependent
RT carboxylases.";
RL Mitochondrion 13:705-720(2013).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 481-1178 IN COMPLEX WITH PYRUVATE;
RP MANGANESE AND BIOTIN ANALOG, CARBOXYLATION AT LYS-741, MUTAGENESIS OF
RP PHE-1077, AND SUBUNIT.
RX PubMed=18297087; DOI=10.1038/nsmb.1393;
RA Xiang S., Tong L.;
RT "Crystal structures of human and Staphylococcus aureus pyruvate carboxylase
RT and molecular insights into the carboxyltransfer reaction.";
RL Nat. Struct. Mol. Biol. 15:295-302(2008).
RN [15]
RP VARIANTS PC DEFICIENCY THR-610 AND ILE-743.
RX PubMed=9585612; DOI=10.1086/301884;
RA Carbone M.A., MacKay N., Ling M., Cole D.E.C., Douglas C., Rigat B.,
RA Feigenbaum A., Clarke J.T.R., Haworth J.C., Greenberg C.R., Seargeant L.,
RA Robinson B.H.;
RT "Amerindian pyruvate carboxylase deficiency is associated with two distinct
RT missense mutations.";
RL Am. J. Hum. Genet. 62:1312-1319(1998).
RN [16]
RP VARIANTS PC DEFICIENCY ALA-145 AND CYS-451, FUNCTION, CATALYTIC ACTIVITY,
RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANTS PC DEFICIENCY ALA-145
RP AND CYS-451, AND COFACTOR.
RX PubMed=9585002; DOI=10.1203/00006450-199805000-00004;
RA Wexler I.D., Kerr D.S., Du Y., Kaung M.M., Stephenson W., Lusk M.M.,
RA Wappner R.S., Higgins J.J.;
RT "Molecular characterization of pyruvate carboxylase deficiency in two
RT consanguineous families.";
RL Pediatr. Res. 43:579-584(1998).
RN [17]
RP VARIANTS PC DEFICIENCY ALA-145; GLN-156; TRP-270; CYS-304; CYS-451;
RP LEU-583; THR-610; GLN-631; ILE-743 AND 1131-VAL--LYS-1133 DEL.
RX PubMed=19306334; DOI=10.1002/humu.20908;
RA Monnot S., Serre V., Chadefaux-Vekemans B., Aupetit J., Romano S.,
RA De Lonlay P., Rival J.-M., Munnich A., Steffann J., Bonnefont J.-P.;
RT "Structural insights on pathogenic effects of novel mutations causing
RT pyruvate carboxylase deficiency.";
RL Hum. Mutat. 30:734-740(2009).
CC -!- FUNCTION: Pyruvate carboxylase catalyzes a 2-step reaction, involving
CC the ATP-dependent carboxylation of the covalently attached biotin in
CC the first step and the transfer of the carboxyl group to pyruvate in
CC the second. Catalyzes in a tissue specific manner, the initial
CC reactions of glucose (liver, kidney) and lipid (adipose tissue, liver,
CC brain) synthesis from pyruvate. {ECO:0000269|PubMed:9585002}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hydrogencarbonate + pyruvate = ADP + H(+) + oxaloacetate
CC + phosphate; Xref=Rhea:RHEA:20844, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16452, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=6.4.1.1;
CC Evidence={ECO:0000269|PubMed:9585002};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20845;
CC Evidence={ECO:0000269|PubMed:9585002};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000269|PubMed:18297087};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000269|PubMed:18297087};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000305|PubMed:9585002}.
CC -!- SUBUNIT: Homotetramer (PubMed:18297087). Interacts (via the biotin
CC carboxylation domain) with SIRT4 (PubMed:23438705).
CC {ECO:0000269|PubMed:18297087, ECO:0000269|PubMed:23438705}.
CC -!- INTERACTION:
CC P11498; P48163: ME1; NbExp=14; IntAct=EBI-2211322, EBI-11958484;
CC P11498; P11498: PC; NbExp=4; IntAct=EBI-2211322, EBI-2211322;
CC P11498; PRO_0000278740 [Q03463]; Xeno; NbExp=7; IntAct=EBI-2211322, EBI-8803426;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:9585002}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P11498-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P11498-2; Sequence=VSP_056358, VSP_056359;
CC -!- PTM: Acetylation of Lys-748 might play a role in catalytic activity
CC regulation. {ECO:0000250|UniProtKB:Q05920}.
CC -!- DISEASE: Pyruvate carboxylase deficiency (PC deficiency) [MIM:266150]:
CC Leads to lactic acidosis, intellectual disability and death. It occurs
CC in three forms: mild or type A, severe neonatal or type B, and a very
CC mild lacticacidemia. {ECO:0000269|PubMed:19306334,
CC ECO:0000269|PubMed:9585002, ECO:0000269|PubMed:9585612}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Pyruvate carboxylase entry;
CC URL="https://en.wikipedia.org/wiki/Pyruvate_carboxylase";
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DR EMBL; U04641; AAA99537.1; -; mRNA.
DR EMBL; S72370; AAB31500.1; -; mRNA.
DR EMBL; U30891; AAA82937.1; -; mRNA.
DR EMBL; AK297705; BAG60062.1; -; mRNA.
DR EMBL; AP000485; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011617; AAH11617.1; -; mRNA.
DR EMBL; M26122; AAA36423.1; -; mRNA.
DR EMBL; K02282; AAA60033.1; -; mRNA.
DR CCDS; CCDS8152.1; -. [P11498-1]
DR PIR; G01933; JC2460.
DR RefSeq; NP_000911.2; NM_000920.3. [P11498-1]
DR RefSeq; NP_001035806.1; NM_001040716.1. [P11498-1]
DR RefSeq; NP_071504.2; NM_022172.2. [P11498-1]
DR RefSeq; XP_005274088.1; XM_005274031.4. [P11498-1]
DR RefSeq; XP_005274089.1; XM_005274032.4. [P11498-1]
DR RefSeq; XP_006718641.1; XM_006718578.3. [P11498-1]
DR RefSeq; XP_011543388.1; XM_011545086.2. [P11498-1]
DR RefSeq; XP_016873357.1; XM_017017868.1. [P11498-1]
DR RefSeq; XP_016873358.1; XM_017017869.1. [P11498-1]
DR RefSeq; XP_016873359.1; XM_017017870.1. [P11498-1]
DR RefSeq; XP_016873360.1; XM_017017871.1. [P11498-1]
DR RefSeq; XP_016873361.1; XM_017017872.1. [P11498-1]
DR PDB; 3BG3; X-ray; 2.80 A; A/B/C/D=482-1178.
DR PDB; 3BG9; X-ray; 3.00 A; A/B/C/D=482-1178.
DR PDBsum; 3BG3; -.
DR PDBsum; 3BG9; -.
DR AlphaFoldDB; P11498; -.
DR SMR; P11498; -.
DR BioGRID; 111124; 152.
DR ComplexPortal; CPX-7142; Hydride transfer complex.
DR DIP; DIP-46372N; -.
DR IntAct; P11498; 41.
DR MINT; P11498; -.
DR STRING; 9606.ENSP00000377532; -.
DR DrugBank; DB07497; 5-(hexahydro-2-oxo-1H-thieno[3,4-D]imidazol-6-yl)pentanal.
DR DrugBank; DB00121; Biotin.
DR DrugBank; DB00119; Pyruvic acid.
DR GlyGen; P11498; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P11498; -.
DR PhosphoSitePlus; P11498; -.
DR SwissPalm; P11498; -.
DR BioMuta; PC; -.
DR DMDM; 1709947; -.
DR EPD; P11498; -.
DR jPOST; P11498; -.
DR MassIVE; P11498; -.
DR MaxQB; P11498; -.
DR PaxDb; P11498; -.
DR PeptideAtlas; P11498; -.
DR PRIDE; P11498; -.
DR ProteomicsDB; 4659; -.
DR ProteomicsDB; 52785; -. [P11498-1]
DR Antibodypedia; 30264; 368 antibodies from 37 providers.
DR DNASU; 5091; -.
DR Ensembl; ENST00000393955.6; ENSP00000377527.2; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000393958.7; ENSP00000377530.2; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000393960.7; ENSP00000377532.1; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000524491.6; ENSP00000434192.2; ENSG00000173599.15. [P11498-2]
DR Ensembl; ENST00000529047.6; ENSP00000435905.2; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000651036.1; ENSP00000498406.1; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000651854.1; ENSP00000498994.1; ENSG00000173599.15. [P11498-1]
DR Ensembl; ENST00000652125.1; ENSP00000498302.1; ENSG00000173599.15. [P11498-1]
DR GeneID; 5091; -.
DR KEGG; hsa:5091; -.
DR MANE-Select; ENST00000393960.7; ENSP00000377532.1; NM_001040716.2; NP_001035806.1.
DR UCSC; uc001ojn.2; human. [P11498-1]
DR CTD; 5091; -.
DR DisGeNET; 5091; -.
DR GeneCards; PC; -.
DR GeneReviews; PC; -.
DR HGNC; HGNC:8636; PC.
DR HPA; ENSG00000173599; Tissue enhanced (adipose tissue, liver).
DR MalaCards; PC; -.
DR MIM; 266150; phenotype.
DR MIM; 608786; gene.
DR neXtProt; NX_P11498; -.
DR OpenTargets; ENSG00000173599; -.
DR Orphanet; 353320; Pyruvate carboxylase deficiency, benign type.
DR Orphanet; 353308; Pyruvate carboxylase deficiency, infantile type.
DR Orphanet; 353314; Pyruvate carboxylase deficiency, severe neonatal type.
DR PharmGKB; PA32975; -.
DR VEuPathDB; HostDB:ENSG00000173599; -.
DR eggNOG; KOG0369; Eukaryota.
DR GeneTree; ENSGT00900000141164; -.
DR HOGENOM; CLU_000395_0_1_1; -.
DR InParanoid; P11498; -.
DR OMA; TRWIESD; -.
DR PhylomeDB; P11498; -.
DR TreeFam; TF300535; -.
DR BioCyc; MetaCyc:HS10697-MON; -.
DR BRENDA; 6.4.1.1; 2681.
DR PathwayCommons; P11498; -.
DR Reactome; R-HSA-196780; Biotin transport and metabolism.
DR Reactome; R-HSA-3371599; Defective HLCS causes multiple carboxylase deficiency.
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR SABIO-RK; P11498; -.
DR SignaLink; P11498; -.
DR SIGNOR; P11498; -.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 5091; 260 hits in 1080 CRISPR screens.
DR ChiTaRS; PC; human.
DR EvolutionaryTrace; P11498; -.
DR GenomeRNAi; 5091; -.
DR Pharos; P11498; Tbio.
DR PRO; PR:P11498; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P11498; protein.
DR Bgee; ENSG00000173599; Expressed in right lobe of liver and 130 other tissues.
DR ExpressionAtlas; P11498; baseline and differential.
DR Genevisible; P11498; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:AgBase.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; TAS:ProtInc.
DR GO; GO:0009374; F:biotin binding; TAS:ProtInc.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004736; F:pyruvate carboxylase activity; IMP:UniProtKB.
DR GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006734; P:NADH metabolic process; IDA:ComplexPortal.
DR GO; GO:0006739; P:NADP metabolic process; IDA:ComplexPortal.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:AgBase.
DR GO; GO:0044794; P:positive regulation by host of viral process; IMP:AgBase.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR GO; GO:0019076; P:viral release from host cell; IMP:AgBase.
DR GO; GO:0019074; P:viral RNA genome packaging; IMP:AgBase.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR005481; BC-like_N.
DR InterPro; IPR001882; Biotin_BS.
DR InterPro; IPR011764; Biotin_carboxylation_dom.
DR InterPro; IPR005482; Biotin_COase_C.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR003379; Carboxylase_cons_dom.
DR InterPro; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
DR InterPro; IPR000891; PYR_CT.
DR InterPro; IPR005930; Pyruv_COase.
DR InterPro; IPR011054; Rudment_hybrid_motif.
DR InterPro; IPR011053; Single_hybrid_motif.
DR Pfam; PF02785; Biotin_carb_C; 1.
DR Pfam; PF00289; Biotin_carb_N; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR Pfam; PF02786; CPSase_L_D2; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR Pfam; PF02436; PYC_OADA; 1.
DR PIRSF; PIRSF001594; Pyruv_carbox; 1.
DR SMART; SM00878; Biotin_carb_C; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 1.
DR TIGRFAMs; TIGR01235; pyruv_carbox; 1.
DR PROSITE; PS50975; ATP_GRASP; 1.
DR PROSITE; PS50979; BC; 1.
DR PROSITE; PS00188; BIOTIN; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Biotin;
KW Disease variant; Gluconeogenesis; Ligase; Lipid biosynthesis;
KW Lipid metabolism; Manganese; Metal-binding; Mitochondrion;
KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein; Pyruvate;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..20
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 21..1178
FT /note="Pyruvate carboxylase, mitochondrial"
FT /id="PRO_0000002840"
FT DOMAIN 36..486
FT /note="Biotin carboxylation"
FT DOMAIN 156..353
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 563..832
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT DOMAIN 1109..1178
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT ACT_SITE 328
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 571..575
FT /ligand="substrate"
FT BINDING 572
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:18297087"
FT BINDING 644
FT /ligand="substrate"
FT BINDING 741
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /note="via carbamate group"
FT /evidence="ECO:0000269|PubMed:18297087"
FT BINDING 771
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:18297087"
FT BINDING 773
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:18297087"
FT BINDING 908
FT /ligand="substrate"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 39
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 79
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 79
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 148
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 297
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 319
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 434
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 442
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 589
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 661
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 717
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 741
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000269|PubMed:18297087"
FT MOD_RES 748
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 892
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 969
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 992
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 1003
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P52873"
FT MOD_RES 1061
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 1090
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 1144
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000269|PubMed:6548474, ECO:0000269|PubMed:7918683"
FT VAR_SEQ 457..529
FT /note="TNIAFLQNVLNNQQFLAGTVDTQFIDENPELFQLRPAQNRAQKLLHYLGHVM
FT VNGPTTPIPVKASPSPTDPVV -> VRRHQAQPLAAALGRPCGQEARRPQAAVTAPTGP
FT GSPTLVRVPPAARVLSSRLGGPSQTTPETSTEVSPTILL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056358"
FT VAR_SEQ 530..1178
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056359"
FT VARIANT 76
FT /note="H -> L (in dbSNP:rs7104156)"
FT /id="VAR_048416"
FT VARIANT 145
FT /note="V -> A (in PC deficiency; mild; strongly reduced
FT pyruvate carboxylase activity; dbSNP:rs28940591)"
FT /evidence="ECO:0000269|PubMed:19306334,
FT ECO:0000269|PubMed:9585002"
FT /id="VAR_015199"
FT VARIANT 156
FT /note="R -> Q (in PC deficiency; dbSNP:rs119103241)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058957"
FT VARIANT 270
FT /note="R -> W (in PC deficiency; dbSNP:rs1258494752)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058958"
FT VARIANT 304
FT /note="Y -> C (in PC deficiency)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058959"
FT VARIANT 451
FT /note="R -> C (in PC deficiency; mild; strongly reduced
FT pyruvate carboxylase activity; dbSNP:rs113994143)"
FT /evidence="ECO:0000269|PubMed:19306334,
FT ECO:0000269|PubMed:9585002"
FT /id="VAR_015200"
FT VARIANT 583
FT /note="R -> L (in PC deficiency; dbSNP:rs119103242)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058960"
FT VARIANT 610
FT /note="A -> T (in PC deficiency; mild; dbSNP:rs28940589)"
FT /evidence="ECO:0000269|PubMed:19306334,
FT ECO:0000269|PubMed:9585612"
FT /id="VAR_008095"
FT VARIANT 631
FT /note="R -> Q (in PC deficiency; dbSNP:rs113994145)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058961"
FT VARIANT 743
FT /note="M -> I (in PC deficiency; mild; dbSNP:rs28940590)"
FT /evidence="ECO:0000269|PubMed:19306334,
FT ECO:0000269|PubMed:9585612"
FT /id="VAR_008096"
FT VARIANT 1131..1133
FT /note="Missing (in PC deficiency)"
FT /evidence="ECO:0000269|PubMed:19306334"
FT /id="VAR_058962"
FT MUTAGEN 1077
FT /note="F->A,E: Loss of tetramerization and enzyme activity,
FT resulting in an inactive homodimer."
FT /evidence="ECO:0000269|PubMed:18297087"
FT CONFLICT 225..226
FT /note="LA -> WP (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="A -> S (in Ref. 3; AAA82937)"
FT /evidence="ECO:0000305"
FT CONFLICT 385..386
FT /note="RS -> PT (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT CONFLICT 486..487
FT /note="EL -> DV (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT CONFLICT 638
FT /note="P -> R (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT CONFLICT 729
FT /note="E -> A (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT CONFLICT 774..775
FT /note="DT -> AP (in Ref. 2; AAB31500)"
FT /evidence="ECO:0000305"
FT HELIX 495..510
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 541..559
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 569..571
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 572..577
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 584..597
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 602..608
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 611..617
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 623..633
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 635..637
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 639..643
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 645..647
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 650..652
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 656..669
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 673..677
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 683..694
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 695..697
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 698..705
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 720..733
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 736..741
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 749..762
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 768..771
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 779..788
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 792..797
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 799..801
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 810..817
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 828..844
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 845..848
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 850..852
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 861..864
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 868..875
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 876..878
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 879..881
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 886..900
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 910..923
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 928..934
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 935..937
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 942..947
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 948..950
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 961..968
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 969..971
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 978..981
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 989..997
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 1004..1012
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 1014..1026
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 1035..1040
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1047..1051
FT /evidence="ECO:0007829|PDB:3BG3"
FT TURN 1053..1055
FT /evidence="ECO:0007829|PDB:3BG9"
FT STRAND 1057..1068
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1072..1090
FT /evidence="ECO:0007829|PDB:3BG3"
FT HELIX 1092..1094
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1108..1110
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1118..1123
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1138..1144
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1146..1149
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1164..1168
FT /evidence="ECO:0007829|PDB:3BG3"
FT STRAND 1173..1175
FT /evidence="ECO:0007829|PDB:3BG3"
SQ SEQUENCE 1178 AA; 129634 MW; 381F527553A20095 CRC64;
MLKFRTVHGG LRLLGIRRTS TAPAASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG
IRTVAIYSEQ DTGQMHRQKA DEAYLIGRGL APVQAYLHIP DIIKVAKENN VDAVHPGYGF
LSERADFAQA CQDAGVRFIG PSPEVVRKMG DKVEARAIAI AAGVPVVPGT DAPITSLHEA
HEFSNTYGFP IIFKAAYGGG GRGMRVVHSY EELEENYTRA YSEALAAFGN GALFVEKFIE
KPRHIEVQIL GDQYGNILHL YERDCSIQRR HQKVVEIAPA AHLDPQLRTR LTSDSVKLAK
QVGYENAGTV EFLVDRHGKH YFIEVNSRLQ VEHTVTEEIT DVDLVHAQIH VAEGRSLPDL
GLRQENIRIN GCAIQCRVTT EDPARSFQPD TGRIEVFRSG EGMGIRLDNA SAFQGAVISP
HYDSLLVKVI AHGKDHPTAA TKMSRALAEF RVRGVKTNIA FLQNVLNNQQ FLAGTVDTQF
IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVKA SPSPTDPVVP AVPIGPPPAG
FRDILLREGP EGFARAVRNH PGLLLMDTTF RDAHQSLLAT RVRTHDLKKI APYVAHNFSK
LFSMENWGGA TFDVAMRFLY ECPWRRLQEL RELIPNIPFQ MLLRGANAVG YTNYPDNVVF
KFCEVAKENG MDVFRVFDSL NYLPNMLLGM EAAGSAGGVV EAAISYTGDV ADPSRTKYSL
QYYMGLAEEL VRAGTHILCI KDMAGLLKPT ACTMLVSSLR DRFPDLPLHI HTHDTSGAGV
AAMLACAQAG ADVVDVAADS MSGMTSQPSM GALVACTRGT PLDTEVPMER VFDYSEYWEG
ARGLYAAFDC TATMKSGNSD VYENEIPGGQ YTNLHFQAHS MGLGSKFKEV KKAYVEANQM
LGDLIKVTPS SKIVGDLAQF MVQNGLSRAE AEAQAEELSF PRSVVEFLQG YIGVPHGGFP
EPFRSKVLKD LPRVEGRPGA SLPPLDLQAL EKELVDRHGE EVTPEDVLSA AMYPDVFAHF
KDFTATFGPL DSLNTRLFLQ GPKIAEEFEV ELERGKTLHI KALAVSDLNR AGQRQVFFEL
NGQLRSILVK DTQAMKEMHF HPKALKDVKG QIGAPMPGKV IDIKVVAGAK VAKGQPLCVL
SAMKMETVVT SPMEGTVRKV HVTKDMTLEG DDLILEIE
