PYC_RAT
ID PYC_RAT Reviewed; 1178 AA.
AC P52873; Q5RKM0; Q64555;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Pyruvate carboxylase, mitochondrial;
DE EC=6.4.1.1 {ECO:0000250|UniProtKB:P11498};
DE AltName: Full=Pyruvic carboxylase;
DE Short=PCB;
DE Flags: Precursor;
GN Name=Pc;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=8522203; DOI=10.1016/0378-1119(95)00557-m;
RA Lehn D.A., Moran S.M., Macdonald M.J.;
RT "The sequence of the rat pyruvate carboxylase-encoding cDNA.";
RL Gene 165:331-332(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8687410; DOI=10.1042/bj3160631;
RA Jitrapakdee S., Booker G.W., Cassady A.I., Wallace J.C.;
RT "Cloning, sequencing and expression of rat liver pyruvate carboxylase.";
RL Biochem. J. 316:631-637(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP PROTEIN SEQUENCE OF 21-35; 1134-1137 AND 1139-1158.
RC TISSUE=Liver;
RX PubMed=3178228; DOI=10.1016/0003-9861(88)90258-5;
RA Thampy K.G., Huang W.Y., Wakil S.J.;
RT "A rapid purification method for rat liver pyruvate carboxylase and amino
RT acid sequence analyses of NH2-terminal and biotin peptide.";
RL Arch. Biochem. Biophys. 266:270-276(1988).
RN [5]
RP PROTEIN SEQUENCE OF 244-263; 329-355; 407-428 AND 943-964, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (DEC-2006) to UniProtKB.
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1003, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:0000250|UniProtKB:P11498};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20845;
CC Evidence={ECO:0000250|UniProtKB:P11498};
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. Interacts (via the biotin carboxylation domain)
CC with SIRT4. {ECO:0000250|UniProtKB:P11498}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P11498}.
CC -!- PTM: Acetylation of Lys-748 might play a role in catalytic activity
CC regulation. {ECO:0000250|UniProtKB:Q05920}.
CC -!- MISCELLANEOUS: This enzyme performs an important anaplerotic function
CC in replenishing citric acid cycle intermediates that exit the
CC mitochondrion for consumption in various pathways.
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DR EMBL; U32314; AAA96256.1; -; mRNA.
DR EMBL; U36585; AAC52668.1; -; mRNA.
DR EMBL; BC085680; AAH85680.1; -; mRNA.
DR PIR; S68252; JC4391.
DR RefSeq; NP_036876.2; NM_012744.2.
DR RefSeq; XP_006230754.1; XM_006230692.3.
DR RefSeq; XP_006230755.1; XM_006230693.2.
DR RefSeq; XP_006230756.1; XM_006230694.3.
DR AlphaFoldDB; P52873; -.
DR SMR; P52873; -.
DR BioGRID; 247176; 6.
DR IntAct; P52873; 3.
DR MINT; P52873; -.
DR STRING; 10116.ENSRNOP00000026316; -.
DR CarbonylDB; P52873; -.
DR iPTMnet; P52873; -.
DR PhosphoSitePlus; P52873; -.
DR World-2DPAGE; 0004:P52873; -.
DR jPOST; P52873; -.
DR PaxDb; P52873; -.
DR PRIDE; P52873; -.
DR GeneID; 25104; -.
DR KEGG; rno:25104; -.
DR UCSC; RGD:3262; rat.
DR CTD; 5091; -.
DR RGD; 3262; Pc.
DR VEuPathDB; HostDB:ENSRNOG00000019372; -.
DR eggNOG; KOG0369; Eukaryota.
DR HOGENOM; CLU_000395_1_0_1; -.
DR InParanoid; P52873; -.
DR PhylomeDB; P52873; -.
DR TreeFam; TF300535; -.
DR BRENDA; 6.4.1.1; 5301.
DR Reactome; R-RNO-196780; Biotin transport and metabolism.
DR Reactome; R-RNO-70263; Gluconeogenesis.
DR UniPathway; UPA00138; -.
DR PRO; PR:P52873; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019372; Expressed in adult mammalian kidney and 19 other tissues.
DR ExpressionAtlas; P52873; baseline and differential.
DR Genevisible; P52873; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0009374; F:biotin binding; IDA:RGD.
DR GO; GO:0031406; F:carboxylic acid binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004736; F:pyruvate carboxylase activity; IDA:RGD.
DR GO; GO:0006094; P:gluconeogenesis; IDA:RGD.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IDA:RGD.
DR GO; GO:0044794; P:positive regulation by host of viral process; ISO:RGD.
DR GO; GO:0071073; P:positive regulation of phospholipid biosynthetic process; IMP:CACAO.
DR GO; GO:0006090; P:pyruvate metabolic process; IDA:RGD.
DR GO; GO:0019076; P:viral release from host cell; ISO:RGD.
DR GO; GO:0019074; P:viral RNA genome packaging; ISO:RGD.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.30.1490.20; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR011761; ATP-grasp.
DR InterPro; IPR013815; ATP_grasp_subdomain_1.
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; Direct protein sequencing;
KW Gluconeogenesis; Ligase; Lipid biosynthesis; Lipid metabolism; Manganese;
KW Metal-binding; Mitochondrion; Multifunctional enzyme; Nucleotide-binding;
KW Phosphoprotein; 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_0000002842"
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 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 316
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:0000250"
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 988
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q05920"
FT MOD_RES 988
FT /note="N6-succinyllysine; alternate"
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:0007744|PubMed:22673903"
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:0000250|UniProtKB:P11498"
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:0000250, ECO:0000255|PROSITE-
FT ProRule:PRU01066"
FT CONFLICT 21..22
FT /note="TA -> SG (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 26..27
FT /note="SP -> PL (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 30..31
FT /note="RR -> LL (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 35
FT /note="K -> P (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="S -> P (in Ref. 1; AAA96256)"
FT /evidence="ECO:0000305"
FT CONFLICT 866
FT /note="I -> D (in Ref. 1; AAA96256)"
FT /evidence="ECO:0000305"
FT CONFLICT 977
FT /note="R -> G (in Ref. 1; AAA96256)"
FT /evidence="ECO:0000305"
FT CONFLICT 1135
FT /note="Q -> A (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 1153
FT /note="M -> T (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1178 AA; 129777 MW; 782CDFEF3380DB2D CRC64;
MLKFQTVRGG LRLLGVRRSS TAPVASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG
IRTVAVYSEQ DTGQMHRQKA DEAYLIGRGL APVQAYLHIP DIIKVAKENG VDAVHPGYGF
LSERADFAQA CQDAGVRFIG PSPEVVRKMG DKVEARAIAI AAGVPVVPGT NSPINSLHEA
HEFSNTYGFP 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 FLAGIVDTQF
IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVKV SPSPVDPIVP VVPIGPPPAG
FRDILLREGP EGFARAVRNH QGLLLMDTTF RDAHQSLLAT RVRTHDLKKI APYVAHNFNN
LFSIENWGGA TFDVAMRFLY ECPWRRLQEL RELIPNIPFQ MLLRGANAVG YTNYPDNVVF
KFCEVAKENG MDVFRIFDSL NYLPNMLLGM EAAGSAGGVV EAAISYTGDV ADPSRTKYSL
EYYMGLAEEL VRAGTHILCI KDMAGLLKPA ACTMLVSSLR DRFPDLPLHI HTHDTSGSGV
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 IDVKVAAGAK VVKGQPLCVL
SAMKMETVVT SPMEGTIRKV HVTKDMTLEG DDLILEIE