PCCA_RAT
ID PCCA_RAT Reviewed; 737 AA.
AC P14882;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Propionyl-CoA carboxylase alpha chain, mitochondrial {ECO:0000305|PubMed:2745462};
DE Short=PCCase subunit alpha;
DE EC=6.4.1.3 {ECO:0000250|UniProtKB:P05165};
DE AltName: Full=Propanoyl-CoA:carbon dioxide ligase subunit alpha;
DE Flags: Precursor;
GN Name=Pcca {ECO:0000312|RGD:3264};
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] OF 1-33.
RC TISSUE=Uterus;
RX PubMed=15060005; DOI=10.1101/gr.1932304;
RA Vitt U., Gietzen D., Stevens K., Wingrove J., Becha S., Bulloch S.,
RA Burrill J., Chawla N., Chien J., Crawford M., Ison C., Kearney L.,
RA Kwong M., Park J., Policky J., Weiler M., White R., Xu Y., Daniels S.,
RA Jacob H., Jensen-Seaman M.I., Lazar J., Stuve L., Schmidt J.;
RT "Identification of candidate disease genes by EST alignments, synteny, and
RT expression and verification of Ensembl genes on rat chromosome 1q43-54.";
RL Genome Res. 14:640-650(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 34-737.
RX PubMed=2745462; DOI=10.1016/s0021-9258(18)63910-9;
RA Browner M.F., Taroni F., Sztul E., Rosenberg L.E.;
RT "Sequence analysis, biogenesis, and mitochondrial import of the alpha-
RT subunit of rat liver propionyl-CoA carboxylase.";
RL J. Biol. Chem. 264:12680-12685(1989).
RN [3]
RP SEQUENCE REVISION.
RA Browner M.F., Taroni F., Sztul E., Rosenberg L.E.;
RL Submitted (FEB-1989) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 143-159; 353-387; 426-439; 475-485; 512-522 AND
RP 532-548, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RA Lubec G., Diao W.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, 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: 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 Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-
CC CoA/propanoyl-CoA to D-methylmalonyl-CoA/(S)-methylmalonyl-CoA (By
CC similarity). Within the holoenzyme, the alpha subunit catalyzes the
CC ATP-dependent carboxylation of the biotin carried by the biotin
CC carboxyl carrier (BCC) domain, while the beta subunit then transfers
CC the carboxyl group from carboxylated biotin to propionyl-CoA (By
CC similarity). Propionyl-CoA carboxylase also significantly acts on
CC butyryl-CoA/butanoyl-CoA, which is converted to ethylmalonyl-CoA/(2S)-
CC ethylmalonyl-CoA (By similarity). Other alternative minor substrates
CC include (2E)-butenoyl-CoA/crotonoyl-CoA (By similarity).
CC {ECO:0000250|UniProtKB:P05165, ECO:0000250|UniProtKB:P0DTA4,
CC ECO:0000250|UniProtKB:Q5LUF3}.
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:0000250|UniProtKB:P05165};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721;
CC Evidence={ECO:0000250|UniProtKB:P05165};
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:0000250|UniProtKB:P0DTA4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59521;
CC Evidence={ECO:0000250|UniProtKB:P0DTA4};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01066};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00409,
CC ECO:0000255|PROSITE-ProRule:PRU00969};
CC Note=Binds 2 magnesium or manganese ions per subunit.
CC {ECO:0000255|PROSITE-ProRule:PRU00409, ECO:0000255|PROSITE-
CC ProRule:PRU00969};
CC -!- PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation;
CC succinyl-CoA from propanoyl-CoA: step 1/3.
CC {ECO:0000250|UniProtKB:P05165}.
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:0000250|UniProtKB:P05165}.
CC -!- DOMAIN: Consists of an N-terminal biotin carboxylation/carboxylase (BC)
CC domain that catalyzes the transient carboxylation of the biotin
CC covalently attached to the C-terminal biotinyl-binding/biotin carboxyl
CC carrier (BCC) domain. {ECO:0000250|UniProtKB:Q5LUF3}.
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.
CC Biotinylation is catalyzed by HLCS. {ECO:0000250|UniProtKB:P05165}.
CC -!- DISEASE: Note=Propionic acidemia due to recessively inherited
CC deficiency of PCCase activity often causes life-threatening ketosis and
CC acidosis.
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DR EMBL; CK228512; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; M22631; AAA88512.1; ALT_SEQ; mRNA.
DR PIR; A34337; A34337.
DR RefSeq; NP_062203.1; NM_019330.1.
DR AlphaFoldDB; P14882; -.
DR SMR; P14882; -.
DR BioGRID; 601858; 2.
DR iPTMnet; P14882; -.
DR PhosphoSitePlus; P14882; -.
DR jPOST; P14882; -.
DR PRIDE; P14882; -.
DR GeneID; 687008; -.
DR KEGG; rno:687008; -.
DR CTD; 5095; -.
DR RGD; 3264; Pcca.
DR eggNOG; KOG0238; Eukaryota.
DR InParanoid; P14882; -.
DR OrthoDB; 254436at2759; -.
DR PhylomeDB; P14882; -.
DR BioCyc; MetaCyc:MON-8606; -.
DR BRENDA; 6.4.1.3; 5301.
DR Reactome; R-RNO-196780; Biotin transport and metabolism.
DR Reactome; R-RNO-71032; Propionyl-CoA catabolism.
DR UniPathway; UPA00945; UER00908.
DR PRO; PR:P14882; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:1902494; C:catalytic complex; ISO:RGD.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004658; F:propionyl-CoA carboxylase activity; ISS:UniProtKB.
DR GO; GO:0009063; P:cellular amino acid catabolic process; TAS:RGD.
DR GO; GO:0009062; P:fatty acid catabolic process; TAS:RGD.
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; Direct protein sequencing; Ligase;
KW Lipid degradation; Lipid metabolism; Magnesium; Manganese; Metal-binding;
KW Mitochondrion; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..61
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 62..737
FT /note="Propionyl-CoA carboxylase alpha chain,
FT mitochondrial"
FT /id="PRO_0000002839"
FT DOMAIN 71..518
FT /note="Biotin carboxylation"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00969"
FT DOMAIN 190..387
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 658..737
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT ACT_SITE 362
FT /evidence="ECO:0000250"
FT BINDING 186
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 218..279
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT BINDING 270
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 305
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 345
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 345
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 358
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 358
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 358
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 358
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 360
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 360
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409,
FT ECO:0000255|PROSITE-ProRule:PRU00969"
FT BINDING 418
FT /ligand="biotin"
FT /ligand_id="ChEBI:CHEBI:57586"
FT /evidence="ECO:0000250|UniProtKB:Q5LUF3"
FT MOD_RES 74
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 74
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 128
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 159
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 159
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 163
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 197
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 209
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 209
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 271
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 337
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 337
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 394
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 416
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 505
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 511
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 522
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 567
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 657
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 703
FT /note="N6-biotinyllysine; by HLCS"
FT /evidence="ECO:0000250|UniProtKB:P05165,
FT ECO:0000255|PROSITE-ProRule:PRU01066"
SQ SEQUENCE 737 AA; 81623 MW; 58D13E5033A1D024 CRC64;
MAGLWVRTVA LLAARRHWRR SSQQLLWTLK RAPRSSQQLL WTLKRAPVYS QQCLVVSRSL
SSVEYEPKEK TFDKILIANR GEIACRVIKT CRKMGIRTVA IHSDVDASSV HVKMADEAVC
VGPAPTSKSY LNMDAIMEAI KKTGAQAVHP GYGFLSENKE FAKCLAAEDV TFIGPDTHAI
QAMGDKIESK LLAKRAKVNT IPGFDGVLKD ADEAVRIARE IGYPVMIKAS AGGGGKGMRI
PWDDEETRDG FRFSSQEAAS SFGDDRLLIE KFIDNPRHIE IQVLGDKHGN ALWLNERECS
IQRRNQKVVE EAPSIFLDPE TRRAMGEQAV AWPKAVKYSS AGTVEFLVDS QKNFYFLEMN
TRLQVEHPVT ECITGLDLVQ EMILVAKGYP LRHKQEDIPI SGWAVECRVY AEDPYKSFGL
PSIGRLSQYQ EPIHLPGVRV DSGIQPGSDI SIYHDPMISK LVTYGSDRAE ALKRMEDALD
SYVIRGVTHN IPLLREVIIN TRFVKGDIST KFLSDVYPDG FKGHMLTPSE RDQLLAIASS
LFVASQLRAQ RFQEHSRVPV IRPDVAKWEL SVKLHDEDHT VVASNNGPTF NVEVDGSKLN
VTSTWNLASP LLSVNVDGTQ RTVQCLSPDA GGNMSIQFLG TVYKVHILTK LAAELNKFML
EKVPKDTSSV LRSPKPGVVV AVSVKPGDMV AEGQEICVIE AMKMQNSMTA GKMGKVKLVH
CKAGDTVGEG DLLVELE
