PYC_MOUSE
ID PYC_MOUSE Reviewed; 1178 AA.
AC Q05920;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Pyruvate carboxylase, mitochondrial;
DE EC=6.4.1.1 {ECO:0000305|PubMed:23438705};
DE AltName: Full=Pyruvic carboxylase;
DE Short=PCB;
DE Flags: Precursor;
GN Name=Pc; Synonyms=Pcx;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adipocyte;
RX PubMed=8446588; DOI=10.1073/pnas.90.5.1766;
RA Zhang J., Xia W.L., Brew K., Ahmad F.;
RT "Adipose pyruvate carboxylase: amino acid sequence and domain structure
RT deduced from cDNA sequencing.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:1766-1770(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP CATALYTIC ACTIVITY, INTERACTION WITH SIRT4, ACETYLATION AT LYS-35; LYS-39;
RP LYS-79; LYS-148; LYS-152; LYS-241; LYS-434; LYS-589; LYS-717; LYS-748;
RP LYS-892; LYS-969 AND LYS-992, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF LYS-79; LYS-152 AND LYS-748.
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 [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-79; LYS-442 AND LYS-988, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-79; LYS-297; LYS-316; LYS-319;
RP LYS-434; LYS-661; LYS-748; LYS-988; LYS-992; LYS-1061; LYS-1090 AND
RP LYS-1124, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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:0000250|UniProtKB:P11498}.
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:0000305|PubMed:23438705};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20845;
CC Evidence={ECO:0000305|PubMed:23438705};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000250|UniProtKB:P11498};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P11498};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000250|UniProtKB:P11498};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000250|UniProtKB:P11498}.
CC -!- SUBUNIT: Homotetramer (By similarity). Interacts (via the biotin
CC carboxylation domain) with SIRT4 (PubMed:23438705).
CC {ECO:0000250|UniProtKB:P11498, ECO:0000269|PubMed:23438705}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P11498}.
CC -!- TISSUE SPECIFICITY: Liver, kidney, adipose tissue, liver and brain.
CC -!- PTM: Acetylation of Lys-316 is observed in liver mitochondria from
CC fasted mice but not from fed mice (PubMed:23576753). Acetylation of
CC Lys-748 might play a role in catalytic activity regulation
CC (PubMed:23438705). {ECO:0000269|PubMed:23438705}.
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DR EMBL; L09192; AAA39737.1; -; mRNA.
DR EMBL; BC055030; AAH55030.1; -; mRNA.
DR CCDS; CCDS29430.1; -.
DR PIR; A47255; A47255.
DR AlphaFoldDB; Q05920; -.
DR SMR; Q05920; -.
DR IntAct; Q05920; 5.
DR MINT; Q05920; -.
DR STRING; 10090.ENSMUSP00000063825; -.
DR CarbonylDB; Q05920; -.
DR iPTMnet; Q05920; -.
DR PhosphoSitePlus; Q05920; -.
DR SwissPalm; Q05920; -.
DR REPRODUCTION-2DPAGE; Q05920; -.
DR SWISS-2DPAGE; Q05920; -.
DR EPD; Q05920; -.
DR jPOST; Q05920; -.
DR MaxQB; Q05920; -.
DR PaxDb; Q05920; -.
DR PeptideAtlas; Q05920; -.
DR PRIDE; Q05920; -.
DR ProteomicsDB; 300363; -.
DR MGI; MGI:97520; Pcx.
DR eggNOG; KOG0369; Eukaryota.
DR InParanoid; Q05920; -.
DR PhylomeDB; Q05920; -.
DR Reactome; R-MMU-196780; Biotin transport and metabolism.
DR Reactome; R-MMU-70263; Gluconeogenesis.
DR UniPathway; UPA00138; -.
DR ChiTaRS; Pcx; mouse.
DR PRO; PR:Q05920; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q05920; protein.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0009374; F:biotin binding; ISO:MGI.
DR GO; GO:0031406; F:carboxylic acid binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004736; F:pyruvate carboxylase activity; IMP:MGI.
DR GO; GO:0006094; P:gluconeogenesis; IMP:MGI.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006734; P:NADH metabolic process; ISO:MGI.
DR GO; GO:0006739; P:NADP metabolic process; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0006107; P:oxaloacetate metabolic process; ISO:MGI.
DR GO; GO:0044794; P:positive regulation by host of viral process; ISO:MGI.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; ISO:MGI.
DR GO; GO:0006090; P:pyruvate metabolic process; ISO:MGI.
DR GO; GO:0019076; P:viral release from host cell; ISO:MGI.
DR GO; GO:0019074; P:viral RNA genome packaging; ISO:MGI.
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 Acetylation; ATP-binding; Biotin; Gluconeogenesis; Ligase;
KW Lipid biosynthesis; Lipid metabolism; Manganese; Metal-binding;
KW Mitochondrion; Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Pyruvate; 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_0000002841"
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 /evidence="ECO:0000250"
FT BINDING 572
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 644
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 741
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /note="via carbamate group"
FT /evidence="ECO:0000250"
FT BINDING 771
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 773
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 908
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 35
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 39
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 79
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:23438705,
FT ECO:0007744|PubMed:23576753"
FT MOD_RES 79
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 148
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 152
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 297
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 316
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 319
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 434
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705,
FT ECO:0007744|PubMed:23576753"
FT MOD_RES 442
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 589
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 661
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 717
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 741
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000250"
FT MOD_RES 748
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705,
FT ECO:0007744|PubMed:23576753"
FT MOD_RES 892
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 969
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:23438705"
FT MOD_RES 988
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 988
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 992
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 1003
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P52873"
FT MOD_RES 1061
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 1090
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 1124
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 1144
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000250, ECO:0000255|PROSITE-
FT ProRule:PRU01066"
FT MUTAGEN 79
FT /note="K->Q,R: Reduced pyruvate carboxylase activity."
FT /evidence="ECO:0000269|PubMed:23438705"
FT MUTAGEN 152
FT /note="K->Q,R: Reduced pyruvate carboxylase activity."
FT /evidence="ECO:0000269|PubMed:23438705"
FT MUTAGEN 748
FT /note="K->Q: Reduced pyruvate carboxylase activity."
FT /evidence="ECO:0000269|PubMed:23438705"
SQ SEQUENCE 1178 AA; 129685 MW; 14CEA0F9DA8B8127 CRC64;
MLKFQTVRGG LRLLGVRRSS SAPVASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG
IRTVAVYSEQ DTGQMHRQKA DEAYLIGRGL APVQAYLHIP DIIKVAKENG VDAVHPGYGF
LSERADFAQA CQDAGVRFIG PSPEVVRKMG DKVEARAIAI AAGVPVVPGT DSPISSLHEA
HEFSNTFGFP IIFKAAYGGG GRGMRVVHSY EELEENYTRA YSEALAAFGN GALFVEKFIE
KPRHIEVQIL GDQYGNILHL YERDCSIQRR HQKVVEIAPA THLDPQLRSR LTSDSVKLAK
QVGYENAGTV EFLVDKHGKH YFIEVNSRLQ VEHTVTEEIT DVDLVHAQIH VSEGRSLPDL
GLRQENIRIN GCAIQCRVTT EDPARSFQPD TGRIEVFRSG EGMGIRLDNA SAFQGAVISP
HYDSLLVKVI AHGKDHPTAA TKMSRALAEF RVRGVKTNIP FLQNVLNNQQ FLAGTVDTQF
IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVNV SPSPVDPAVP VVPIGPPPAG
FRDILLREGP EGFARAVRNH QGLLLMDTTF RDAHQSLLAT RVRTHDLKKI APYVAHNFNK
LFSMENWGGA TFDVAMRFLY ECPWRRLQEL RELIPNIPFQ MLLRGANAVG YTNYPDNVVF
KFCEVAKENG MDVFRVFDSL NYLPNMLLGM EAAGSAGGVV EAAISYTGDV ADPSRTKYSL
EYYMGLAEEL VRAGTHILCI KDMAGLLKPA ACTMLVSSLR DRFPDLPLHI HTHDTSGAGV
AAMLACAQAG ADVVDVAVDS MSGMTSQPSM GALVACTKGT PLDTEVPLER VFDYSEYWEG
ARGLYAAFDC TATMKSGNSD VYENEIPGGQ YTNLHFQAHS MGLGSKFKEV KKAYVEANQM
LGDLIKVTPS SKIVGDLAQF MVQNGLSRAE AEAQAEELSF PRSVVEFLQG YIGIPHGGFP
EPFRSKVLKD LPRIEGRPGA SLPPLNLKEL EKDLIDRHGE EVTPEDVLSA AMYPDVFAQF
KDFTATFGPL DSLNTRLFLQ GPKIAEEFEV ELERGKTLHI KALAVSDLNR AGQRQVFFEL
NGQLRSILVK DTQAMKEMHF HPKALKDVKG QIGAPMPGKV IDIKVAAGDK VAKGQPLCVL
SAMKMETVVT SPMEGTIRKV HVTKDMTLEG DDLILEIE
