PYC_BOVIN
ID PYC_BOVIN Reviewed; 1178 AA.
AC Q29RK2; Q866R1;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 25-JUL-2006, sequence version 2.
DT 03-AUG-2022, entry version 122.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15248600; DOI=10.1081/abio-120037897;
RA Agca C., Bidwell C.A., Donkin S.S.;
RT "Cloning of bovine pyruvate carboxylase and 5' untranslated region
RT variants.";
RL Anim. Biotechnol. 15:47-66(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
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 ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY185595; AAO27903.1; -; mRNA.
DR EMBL; BC114135; AAI14136.1; -; mRNA.
DR RefSeq; NP_808815.2; NM_177946.4.
DR RefSeq; XP_005227045.1; XM_005226988.3.
DR RefSeq; XP_005227046.1; XM_005226989.3.
DR RefSeq; XP_005227047.1; XM_005226990.3.
DR RefSeq; XP_005227048.1; XM_005226991.3.
DR RefSeq; XP_005227049.1; XM_005226992.3.
DR RefSeq; XP_005227050.1; XM_005226993.3.
DR RefSeq; XP_005227051.1; XM_005226994.3.
DR RefSeq; XP_015316738.1; XM_015461252.1.
DR RefSeq; XP_015316739.1; XM_015461253.1.
DR AlphaFoldDB; Q29RK2; -.
DR SMR; Q29RK2; -.
DR STRING; 9913.ENSBTAP00000030027; -.
DR ChEMBL; CHEMBL1641351; -.
DR PaxDb; Q29RK2; -.
DR PeptideAtlas; Q29RK2; -.
DR PRIDE; Q29RK2; -.
DR Ensembl; ENSBTAT00000026258; ENSBTAP00000026258; ENSBTAG00000019700.
DR Ensembl; ENSBTAT00000030039; ENSBTAP00000030027; ENSBTAG00000019700.
DR Ensembl; ENSBTAT00000068219; ENSBTAP00000058830; ENSBTAG00000019700.
DR Ensembl; ENSBTAT00000081699; ENSBTAP00000067685; ENSBTAG00000019700.
DR Ensembl; ENSBTAT00000086901; ENSBTAP00000069242; ENSBTAG00000019700.
DR GeneID; 338471; -.
DR KEGG; bta:338471; -.
DR CTD; 5091; -.
DR VEuPathDB; HostDB:ENSBTAG00000019700; -.
DR VGNC; VGNC:56274; PC.
DR eggNOG; KOG0369; Eukaryota.
DR GeneTree; ENSGT00900000141164; -.
DR HOGENOM; CLU_000395_0_1_1; -.
DR InParanoid; Q29RK2; -.
DR OMA; YAIQSRV; -.
DR OrthoDB; 254436at2759; -.
DR TreeFam; TF300535; -.
DR BRENDA; 6.4.1.1; 908.
DR UniPathway; UPA00138; -.
DR PRO; PR:Q29RK2; -.
DR Proteomes; UP000009136; Chromosome 29.
DR Bgee; ENSBTAG00000019700; Expressed in cortex of kidney and 106 other tissues.
DR ExpressionAtlas; Q29RK2; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005743; C:mitochondrial inner membrane; ISS:AgBase.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:AgBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004736; F:pyruvate carboxylase activity; IBA:GO_Central.
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; IEA:Ensembl.
DR GO; GO:0006739; P:NADP metabolic process; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0044794; P:positive regulation by host of viral process; IEA:Ensembl.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR GO; GO:0019076; P:viral release from host cell; IEA:Ensembl.
DR GO; GO:0019074; P:viral RNA genome packaging; IEA:Ensembl.
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 2: Evidence at transcript 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_0000239868"
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 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 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: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 149
FT /note="M -> I (in Ref. 1; AAO27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="A -> T (in Ref. 1; AAO27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="G -> D (in Ref. 1; AAO27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 171
FT /note="D -> N (in Ref. 1; AAO27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="A -> D (in Ref. 1; AAO27903)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="T -> A (in Ref. 2; AAI14136)"
FT /evidence="ECO:0000305"
FT CONFLICT 592
FT /note="P -> L (in Ref. 2; AAI14136)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1178 AA; 129698 MW; 15DDD18BC7920D01 CRC64;
MLKFQTVRGS LRLLAIRRTS TATAASPNVR RLEYKPIKKV MVANRGEIAI RVFRACTELG
IRTVAVYSEQ 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 RVRGVKTNIP FLQNVLNNQQ FLAGTVDTQF
IDENPELFQL RPAQNRAQKL LHYLGHVMVN GPTTPIPVKA SPSPTDPIVP VVPIGPPPTG
FRDILLREGP EGFARAVRNH EGLLLMDTTF RDAHQSLLAT RVRTHDLKKI SPYVAHSFNK
LFSIENWGGA TFDVAMRFLY ECPWRRLQEL RELVPNIPFQ MLLRGANAVG YTNYPDNVVF
KFCEVAKENG MDIFRVFDSL NYLPNLLLGM EAAGSAGGVV EAAISYTGDV SDPSRTKYSL
QYYMGLAEEL VRAGTHILCI KDMAGLLKPT ACTMLVSSLR DRFPDLPLHI HTHDTSGAGV
AAMLACAHAG ADVVDVAADS MSGMTSQPSM GALVACTRGT PLDTGVPLER VFDYSEYWEG
ARGLYAAFDC TATMKSGNSD VYENEIPGGQ YTNLHFQAHS MGLGSKFKEV KKAYVEANQM
LGDLIKVTPS SKIVGDLAQF MVQNGLTRAE AEAQAEELSF PRSVVEFLQG YIGIPHGGFP
EPLRSKVLKD LPRVEGRPGA SLPPLDLQAL EKELTERHGE EVTPEDVLSA AMYPDVFAHF
KDFTATFGPL DSLNTRLFLQ GPKIAEEFEV ELERGKTLHI KALAISDLNR AGQRQVFFEL
NGQLRSILVK DTQAMKEMHF HPKALKDVKG QIGAPMPGKV IDIKVAAGAK VTKGQPLCVL
SAMKMETVVT SPVEGTVRKV HVTKDMTLEG DDLILEIE
