PCCA_PIG
ID PCCA_PIG Reviewed; 730 AA.
AC P0DTA4;
DT 13-NOV-2019, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Propionyl-CoA carboxylase alpha chain, mitochondrial {ECO:0000305|PubMed:13752080};
DE Short=PCCase subunit alpha;
DE EC=6.4.1.3 {ECO:0000269|PubMed:13752080};
DE AltName: Full=Propanoyl-CoA:carbon dioxide ligase subunit alpha;
DE Flags: Precursor;
GN Name=PCCA {ECO:0000250|UniProtKB:P05165};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES,
RP PATHWAY, AND SUBCELLULAR LOCATION.
RX PubMed=13752080;
RA Kaziro Y., Ochoa S., Warner R.C., Chen J.Y.;
RT "Metabolism of propionic acid in animal tissues. VIII. Crystalline
RT propionyl carboxylase.";
RL J. Biol. Chem. 236:1917-1923(1961).
CC -!- FUNCTION: This is one of the 2 subunits of the biotin-dependent
CC propionyl-CoA carboxylase (PCC), a mitochondrial enzyme involved in the
CC catabolism of odd chain fatty acids, branched-chain amino acids
CC isoleucine, threonine, methionine, and valine and other metabolites
CC (PubMed:13752080). Propionyl-CoA carboxylase catalyzes the
CC carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-
CC CoA/(S)-methylmalonyl-CoA (PubMed:13752080). Within the holoenzyme, the
CC alpha subunit catalyzes the ATP-dependent carboxylation of the biotin
CC carried by the biotin carboxyl carrier (BCC) domain, while the beta
CC subunit then tranfers the carboxyl group from carboxylated biotin to
CC propionyl-CoA (By similarity). Propionyl-CoA carboxylase also
CC significantly acts on butyryl-CoA/butanoyl-CoA, which is converted to
CC ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA at a much lower rate
CC (PubMed:13752080). Other alternative minor substrates include (2E)-
CC butenoyl-CoA/crotonoyl-CoA (PubMed:13752080).
CC {ECO:0000250|UniProtKB:Q5LUF3, ECO:0000269|PubMed:13752080}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + hydrogencarbonate + propanoyl-CoA = (S)-methylmalonyl-
CC CoA + ADP + H(+) + phosphate; Xref=Rhea:RHEA:23720,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17544, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57327, ChEBI:CHEBI:57392,
CC ChEBI:CHEBI:456216; EC=6.4.1.3;
CC Evidence={ECO:0000269|PubMed:13752080};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721;
CC Evidence={ECO:0000269|PubMed:13752080};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + butanoyl-CoA + hydrogencarbonate = (2S)-ethylmalonyl-CoA
CC + ADP + H(+) + phosphate; Xref=Rhea:RHEA:59520, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17544, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57371, ChEBI:CHEBI:60909, ChEBI:CHEBI:456216;
CC Evidence={ECO:0000269|PubMed:13752080};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59521;
CC Evidence={ECO:0000269|PubMed:13752080};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01066,
CC ECO:0000269|PubMed:13752080};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.0-8.2 for the propionyl-CoA carboxylase activity.
CC {ECO:0000269|PubMed:13752080};
CC -!- PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation;
CC succinyl-CoA from propanoyl-CoA: step 1/3.
CC {ECO:0000269|PubMed:13752080}.
CC -!- SUBUNIT: The holoenzyme is a dodecamer composed of 6 PCCA/alpha
CC subunits and 6 PCCB/beta subunits. Interacts (via the biotin
CC carboxylation domain) with SIRT4. Interacts with SIRT3 and SIRT5.
CC {ECO:0000250|UniProtKB:P05165}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:13752080}.
CC -!- DOMAIN: Consists of a biotin carboxylase (BC) domain at the amino
CC terminus and a biotinyl-binding/biotin carboxyl carrier(BCC) domain at
CC the carboxyl terminus. {ECO:0000250|UniProtKB:P05165}.
CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:Q91ZA3}.
CC -!- PTM: The biotin cofactor is covalently attached to the C-terminal
CC biotinyl-binding domain and is required for the catalytic activity (By
CC similarity). Biotinylation is catalyzed by HLCS (By similarity).
CC {ECO:0000250|UniProtKB:P05165}.
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DR EMBL; AEMK02000079; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0DTA4; -.
DR SMR; P0DTA4; -.
DR STRING; 9823.ENSSSCP00000010169; -.
DR Ensembl; ENSSSCT00000056816; ENSSSCP00000051580; ENSSSCG00000009522.
DR Ensembl; ENSSSCT00055045036; ENSSSCP00055035879; ENSSSCG00055021858.
DR Ensembl; ENSSSCT00065107014; ENSSSCP00065047653; ENSSSCG00065077149.
DR VGNC; VGNC:91209; PCCA.
DR GeneTree; ENSGT00940000156083; -.
DR Reactome; R-SSC-196780; Biotin transport and metabolism.
DR Reactome; R-SSC-71032; Propionyl-CoA catabolism.
DR UniPathway; UPA00945; UER00908.
DR Proteomes; UP000008227; Chromosome 11.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000009522; Expressed in liver and 46 other tissues.
DR ExpressionAtlas; P0DTA4; baseline and differential.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004658; F:propionyl-CoA carboxylase activity; IDA:UniProtKB.
DR GO; GO:0019626; P:short-chain fatty acid catabolic process; IC:UniProtKB.
DR Gene3D; 3.30.1490.20; -; 1.
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; IPR005479; CbamoylP_synth_lsu-like_ATP-bd.
DR InterPro; IPR041265; PCC_BT.
DR InterPro; IPR016185; PreATP-grasp_dom_sf.
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; PF18140; PCC_BT; 1.
DR SMART; SM00878; Biotin_carb_C; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR SUPFAM; SSF51246; SSF51246; 1.
DR SUPFAM; SSF52440; SSF52440; 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; PS00866; CPSASE_1; 1.
DR PROSITE; PS00867; CPSASE_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Biotin; Ligase; Lipid degradation;
KW Lipid metabolism; Magnesium; Manganese; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transit peptide.
FT TRANSIT 1..52
FT /note="Mitochondrion"
FT /evidence="ECO:0000250|UniProtKB:P05165"
FT CHAIN 53..730
FT /note="Propionyl-CoA carboxylase alpha chain,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000448575"
FT DOMAIN 62..509
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 181..378
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 655..730
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT ACT_SITE 349
FT /evidence="ECO:0000250"
FT BINDING 177
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 209..270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 296
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 336
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 349
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 349
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 349
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 349
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 351
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 351
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 409
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000250|UniProtKB:Q5LUF3"
FT MOD_RES 65
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 65
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 119
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 150
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 150
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 154
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 188
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 200
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 200
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 262
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 407
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 502
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 513
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 650
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 696
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
SQ SEQUENCE 730 AA; 80180 MW; 51FB94B4306DFC0C CRC64;
MAGLWVGGSV LVAAGRRGSR SPRPLMRSVA LWTLKHVPQY SRQRLLVSRS LCLAGYDSNE
KTFDKILIAN RGEIACRVIK TCKKMGIKTV AVHSDVDASS VHVTMADEAV CVGPAPTSKS
YLNMDAIMEA VRTTRAQAVH PGYGFLSENK EFAKCLAAEG VIFIGPDTHA IQAMGDKIES
KLLAKKAKVN TIPGFDGVVK DADEAVRIAR EIGYPVMIKA SAGGGGKGMR IAWDDEETRD
GFRFSSQEAA SSFGDDRLLI EKFIDNPRHI EIQVLGDKHG NALWLNEREC SIQRRNQKVV
EEAPSIFLDS ETRRAMGEQA VALAKAVNYS SAGTVEFLVD SKKNFYFLEM NTRLQVEHPV
TECITGLDLV QEMIRVAKGY PLRHRQADIP INGWAVECRV YAEDPYKSFG LPSIGRLSQY
QEPIHLPGVR VDSGIQPGSD ISIYYDPMIS KLITYGSNRM EALKRMENAL DNYVIRGVTH
NIALLREVII NSRFVEGDIN TKFLSDVYPD GFKGHKLTED ERNQLLAIAS SLFVASQLRA
QRFQEPENSR VPIIKPQVAN WELSIRLHDE VHTVTASNSG PTFSVEVDGS KLNVTSTWNL
ASPLLSVSID GTQRTIQCLS RDAGGNMSIQ FLGTVYKVHI LTKLAAELNK FMLEKAAEDT
SSILHSPMPG VVVAVSVKPG DLVAEGQEIC VIEAMKMQNS MTAGKTGKVK SVHCKAGDTV
GEGDLLVELE
