ID A0A8C8H968_ONCTS Unreviewed; 1138 AA.
AC A0A8C8H968;
DT 19-JAN-2022, integrated into UniProtKB/TrEMBL.
DT 05-FEB-2025, sequence version 2.
DT 28-JAN-2026, entry version 21.
DE RecName: Full=Pyruvate carboxylase {ECO:0000256|PIRNR:PIRNR001594};
DE EC=6.4.1.1 {ECO:0000256|PIRNR:PIRNR001594};
GN Name=pcxa {ECO:0000313|Ensembl:ENSOTSP00005060797.2};
OS Oncorhynchus tshawytscha (Chinook salmon) (Salmo tshawytscha).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Protacanthopterygii; Salmoniformes;
OC Salmonidae; Salmoninae; Oncorhynchus.
OX NCBI_TaxID=74940 {ECO:0000313|Ensembl:ENSOTSP00005060797.2, ECO:0000313|Proteomes:UP000694402};
RN [1] {ECO:0000313|Ensembl:ENSOTSP00005060797.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (AUG-2025) to UniProtKB.
RN [2] {ECO:0000313|Ensembl:ENSOTSP00005060797.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2025) to UniProtKB.
CC -!- FUNCTION: Catalyzes a 2-step reaction, involving the ATP-dependent
CC carboxylation of the covalently attached biotin in the first step and
CC the transfer of the carboxyl group to pyruvate in the second.
CC {ECO:0000256|PIRNR:PIRNR001594}.
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:0000256|ARBA:ARBA00058780}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hydrogencarbonate + pyruvate + ATP = oxaloacetate + ADP +
CC phosphate + H(+); 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:0000256|ARBA:ARBA00051300};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:20845;
CC Evidence={ECO:0000256|ARBA:ARBA00051300};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|ARBA:ARBA00001936};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000256|ARBA:ARBA00001953,
CC ECO:0000256|PIRNR:PIRNR001594};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000256|ARBA:ARBA00004742}.
CC -!- SUBUNIT: Homotetramer. Interacts (via the biotin carboxylation domain)
CC with SIRT4. {ECO:0000256|ARBA:ARBA00064607}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000256|ARBA:ARBA00004305}.
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DR AlphaFoldDB; A0A8C8H968; -.
DR Ensembl; ENSOTST00005066180.2; ENSOTSP00005060797.2; ENSOTSG00005029154.2.
DR GeneTree; ENSGT00900000141164; -.
DR UniPathway; UPA00138; -.
DR Proteomes; UP000694402; Unassembled WGS sequence.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004736; F:pyruvate carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006094; P:gluconeogenesis; IEA:UniProtKB-UniPathway.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR CDD; cd06850; biotinyl_domain; 1.
DR CDD; cd07937; DRE_TIM_PC_TC_5S; 1.
DR FunFam; 2.40.50.100:FF:000003; Acetyl-CoA carboxylase biotin carboxyl carrier protein; 1.
DR FunFam; 3.30.1490.20:FF:000018; Biotin carboxylase; 1.
DR FunFam; 3.10.600.10:FF:000001; Pyruvate carboxylase; 1.
DR FunFam; 3.20.20.70:FF:000033; Pyruvate carboxylase; 1.
DR FunFam; 3.30.470.20:FF:000012; Pyruvate carboxylase; 1.
DR FunFam; 1.10.10.60:FF:000512; Pyruvate carboxylase, mitochondrial; 1.
DR Gene3D; 2.40.50.100; -; 1.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 1.
DR Gene3D; 3.10.600.10; pyruvate carboxylase f1077a mutant domain; 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; CPAse_ATP-bd.
DR InterPro; IPR055268; PCB-like.
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 NCBIfam; NF006761; PRK09282.1; 1.
DR NCBIfam; NF009554; PRK12999.1; 1.
DR NCBIfam; TIGR01235; pyruv_carbox; 1.
DR PANTHER; PTHR43778; PYRUVATE CARBOXYLASE; 1.
DR PANTHER; PTHR43778:SF2; PYRUVATE CARBOXYLASE, MITOCHONDRIAL; 1.
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; SSF51569; Aldolase; 1.
DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding domain-like; 1.
DR SUPFAM; SSF89000; post-HMGL domain-like; 1.
DR SUPFAM; SSF52440; PreATP-grasp domain; 1.
DR SUPFAM; SSF51246; Rudiment single hybrid motif; 1.
DR SUPFAM; SSF51230; Single hybrid motif; 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 4: Predicted;
KW Acetylation {ECO:0000256|ARBA:ARBA00022990};
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PIRNR:PIRNR001594};
KW Biotin {ECO:0000256|ARBA:ARBA00023267, ECO:0000256|PIRNR:PIRNR001594};
KW Gluconeogenesis {ECO:0000256|ARBA:ARBA00022432};
KW Ligase {ECO:0000256|ARBA:ARBA00022598, ECO:0000256|PIRNR:PIRNR001594};
KW Lipid biosynthesis {ECO:0000256|ARBA:ARBA00022516};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW Manganese {ECO:0000256|ARBA:ARBA00023211};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR001594-3};
KW Mitochondrion {ECO:0000256|ARBA:ARBA00023128};
KW Multifunctional enzyme {ECO:0000256|ARBA:ARBA00023268};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|PIRNR:PIRNR001594};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553};
KW Pyruvate {ECO:0000256|ARBA:ARBA00023317};
KW Reference proteome {ECO:0000313|Proteomes:UP000694402};
KW Transit peptide {ECO:0000256|ARBA:ARBA00022946}.
FT DOMAIN 1..445
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000259|PROSITE:PS50979"
FT DOMAIN 115..312
FT /note="ATP-grasp"
FT /evidence="ECO:0000259|PROSITE:PS50975"
FT DOMAIN 522..791
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000259|PROSITE:PS50991"
FT DOMAIN 1068..1137
FT /note="Lipoyl-binding"
FT /evidence="ECO:0000259|PROSITE:PS50968"
FT ACT_SITE 287
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-1"
FT BINDING 111
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-2"
FT BINDING 195
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-2"
FT BINDING 230
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-2"
FT BINDING 531
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-3"
FT BINDING 603
FT /ligand="substrate"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-2"
FT BINDING 700
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /note="via carbamate group"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-3"
FT BINDING 730
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-3"
FT BINDING 732
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-3"
FT BINDING 867
FT /ligand="substrate"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-2"
FT MOD_RES 700
FT /note="N6-carboxylysine"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-4"
FT MOD_RES 1103
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000256|PIRSR:PIRSR001594-4"
SQ SEQUENCE 1138 AA; 125456 MW; 210991EA4BEFA178 CRC64;
TTYYCVYRSG PTLKLSAKVL ESFLSPHNSI PSQMHRQKAD EAYLIGKGLP PVAAYLDIPD
IIKVAKENDV DAIHPGYGFL SERSDFAQAC ADAGVRFIGP SPEVVRKMGD KVEARAIAIR
AGVPVVPGTD GPVTCLSEAQ EFSNTYGFPI IFKAAYGGGG RGMRVVKEYE ELEENYQRAY
SEALAAFGNG ALFVEKFVER PRHIEVQILG DKYGNIIHLY ERDCSIQRRH QKVVEMAPAV
QLDPHLRDRL TADSVNLARQ VGYENAGTVE FLVDKHGRHY FIEVNSRLQV EHTVTEQITD
VDLVHAQLHV CEGRSLPELG LKQDKIRING FAIQCRVTTE DPARGFQPDT GRLEVFRTGE
GMGIRLDSAS AFQGAVISPH YDSLLVKVIA SGNDLPAAAA KMNRALAEFR VRGVKTNIPF
LQNVLSNDQF LYGTVDTQFI DENQELFNLK PVQNRAQKLL HYLGHVMVNG PTTPIPVKAK
PSSIDPVIPP IPLGEPPVGF REVLLREGPE GFAKAVRAHK GLLLMDTTFR DAHQSLLATR
VRTHDLKQVA PFVAHNFSNL FSVENWGGAT FDVAMRFLCE CPWKRLQELR ALLPNVPFQM
LLRGANAVGY TNYPDNAVFK FCEVAKENGM DIFRVFDSLN YLPNLMLGME AAGAAGGVVE
ASISYTGDVS DPMRQKYSLD YYLKLADELV RAGTHILNVK DMAGLLKPES SRMLIGALRD
RFPDMPIHVH THDTAGAGVA AMLACAEAGA DIVDVAVDSM AGMTSQPSMG AIVACTKGTK
FNTGISLENV YDYSEYWEVA RGLYAPFDCT ATMKSGNADV YENEIPGGQY TNLHFQAHSM
GLGHKFKEVK KSYTEANKLL GDLIKVTPSS KIVGDLAQFM VQNSLTRAEV EERADELSFP
LSVVEFLQGH IGIPHGGFPE PFRSKVLKNM PRVEGRPGAS LPAMDFQALE KQLRETHGDD
ITPEDVMSAA MYPKVFQEFK EFTHQFGPVD CLNTRLFLDG PKIAEEFEVE LERGKTLHIK
ALALGDLNKA GQREVFFELN GALRSVLVKD TVAMKEMHFH PKALKDVRGQ VGAPMPGKVV
EVKVKQGQTV EKGQPLCVLT AMKMETVVNS PLSGTVVRIY VNADSSLEGD DLILEITE
//
