GenomeNet

Database: UniProt
Entry: P52873
LinkDB: P52873
Original site: P52873 
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   13-FEB-2019, entry version 168.
DE   RecName: Full=Pyruvate carboxylase, mitochondrial;
DE            EC=6.4.1.1;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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
RT   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
RT   project: 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
RT   amino 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
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Pyruvate carboxylase catalyzes a 2-step reaction,
CC       involving the ATP-dependent carboxylation of the covalently
CC       attached biotin in the first step and the transfer of the carboxyl
CC       group to pyruvate in the second. Catalyzes in a tissue specific
CC       manner, the initial reactions of glucose (liver, kidney) and lipid
CC       (adipose tissue, liver, brain) synthesis from pyruvate.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + hydrogencarbonate + pyruvate = ADP + H(+) +
CC         oxaloacetate + phosphate; Xref=Rhea:RHEA:20844,
CC         ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC         ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:456216; EC=6.4.1.1;
CC   -!- COFACTOR:
CC       Name=biotin; Xref=ChEBI:CHEBI:57586; Evidence={ECO:0000250};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC       Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000250};
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC   -!- SUBUNIT: Homotetramer. Interacts (via the biotin carboxylation
CC       domain) with SIRT4. {ECO:0000250|UniProtKB:P11498,
CC       ECO:0000250|UniProtKB:Q05920}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix.
CC   -!- PTM: Acetylation of Lys-748 might play a role in catalytic
CC       activity regulation. {ECO:0000250|UniProtKB:Q05920}.
CC   -!- MISCELLANEOUS: This enzyme performs an important anaplerotic
CC       function in replenishing citric acid cycle intermediates that exit
CC       the mitochondrion for consumption in various pathways.
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   UniGene; Rn.11094; -.
DR   ProteinModelPortal; P52873; -.
DR   SMR; P52873; -.
DR   BioGrid; 247176; 4.
DR   IntAct; P52873; 1.
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   Ensembl; ENSRNOT00000026316; ENSRNOP00000026316; ENSRNOG00000019372.
DR   Ensembl; ENSRNOT00000082388; ENSRNOP00000075317; ENSRNOG00000019372.
DR   GeneID; 25104; -.
DR   KEGG; rno:25104; -.
DR   UCSC; RGD:3262; rat.
DR   CTD; 5091; -.
DR   RGD; 3262; Pc.
DR   eggNOG; ENOG410IU5D; Eukaryota.
DR   eggNOG; COG1038; LUCA.
DR   GeneTree; ENSGT00900000141164; -.
DR   HOGENOM; HOG000282801; -.
DR   HOVERGEN; HBG008340; -.
DR   InParanoid; P52873; -.
DR   KO; K01958; -.
DR   OrthoDB; 254436at2759; -.
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 10 organ(s), highest expression level in liver.
DR   ExpressionAtlas; P52873; baseline and differential.
DR   Genevisible; P52873; RN.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
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: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:0006107; P:oxaloacetate metabolic process; IDA: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   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; Complete proteome;
KW   Direct protein sequencing; Gluconeogenesis; Ligase;
KW   Lipid biosynthesis; Lipid metabolism; Manganese; Metal-binding;
KW   Mitochondrion; Multifunctional enzyme; Nucleotide-binding;
KW   Phosphoprotein; Pyruvate; Reference proteome; Transit peptide.
FT   TRANSIT       1     20       Mitochondrion. {ECO:0000255}.
FT   CHAIN        21   1178       Pyruvate carboxylase, mitochondrial.
FT                                /FTId=PRO_0000002842.
FT   DOMAIN       36    486       Biotin carboxylation.
FT   DOMAIN      156    353       ATP-grasp. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00409}.
FT   DOMAIN      563    832       Pyruvate carboxyltransferase.
FT                                {ECO:0000255|PROSITE-ProRule:PRU01151}.
FT   DOMAIN     1109   1178       Biotinyl-binding. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01066}.
FT   REGION      571    575       Substrate binding. {ECO:0000250}.
FT   ACT_SITE    328    328       {ECO:0000250}.
FT   METAL       572    572       Manganese. {ECO:0000250}.
FT   METAL       741    741       Manganese; via carbamate group.
FT                                {ECO:0000250}.
FT   METAL       771    771       Manganese. {ECO:0000250}.
FT   METAL       773    773       Manganese. {ECO:0000250}.
FT   BINDING     152    152       ATP. {ECO:0000250}.
FT   BINDING     236    236       ATP. {ECO:0000250}.
FT   BINDING     271    271       ATP. {ECO:0000250}.
FT   BINDING     644    644       Substrate. {ECO:0000250}.
FT   BINDING     908    908       Substrate. {ECO:0000250}.
FT   MOD_RES      35     35       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES      39     39       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES      79     79       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES      79     79       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     148    148       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     152    152       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     241    241       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     297    297       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     316    316       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     319    319       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     434    434       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     442    442       N6-succinyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     589    589       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     661    661       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     717    717       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     741    741       N6-carboxylysine. {ECO:0000250}.
FT   MOD_RES     748    748       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     892    892       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     969    969       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     988    988       N6-acetyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     988    988       N6-succinyllysine; alternate.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES     992    992       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES    1003   1003       Phosphothreonine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES    1061   1061       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES    1090   1090       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:P11498}.
FT   MOD_RES    1124   1124       N6-acetyllysine.
FT                                {ECO:0000250|UniProtKB:Q05920}.
FT   MOD_RES    1144   1144       N6-biotinyllysine. {ECO:0000250,
FT                                ECO:0000255|PROSITE-ProRule:PRU01066}.
FT   CONFLICT     21     22       TA -> SG (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT     26     27       SP -> PL (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT     30     31       RR -> LL (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT     35     35       K -> P (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT    222    222       S -> P (in Ref. 1; AAA96256).
FT                                {ECO:0000305}.
FT   CONFLICT    866    866       I -> D (in Ref. 1; AAA96256).
FT                                {ECO:0000305}.
FT   CONFLICT    977    977       R -> G (in Ref. 1; AAA96256).
FT                                {ECO:0000305}.
FT   CONFLICT   1135   1135       Q -> A (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   CONFLICT   1153   1153       M -> T (in Ref. 4; AA sequence).
FT                                {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
//
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