PCCB_HUMAN
ID PCCB_HUMAN Reviewed; 539 AA.
AC P05166; B7Z2Z4; Q16813; Q96CX0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Propionyl-CoA carboxylase beta chain, mitochondrial {ECO:0000305|PubMed:8188292};
DE Short=PCCase subunit beta;
DE EC=6.4.1.3 {ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947};
DE AltName: Full=Propanoyl-CoA:carbon dioxide ligase subunit beta;
DE Flags: Precursor;
GN Name=PCCB {ECO:0000312|HGNC:HGNC:8654};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-287.
RC TISSUE=Fibroblast, Kidney, and Liver;
RX PubMed=8188292; DOI=10.1006/geno.1994.1099;
RA Lamhonwah A.-M., Leclerc D., Loyer M., Clarizio R., Gravel R.A.;
RT "Correction of the metabolic defect in propionic acidemia fibroblasts by
RT microinjection of a full-length cDNA or RNA transcript encoding the
RT propionyl-CoA carboxylase beta subunit.";
RL Genomics 19:500-505(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver, and Placenta;
RX PubMed=8225321; DOI=10.1007/bf01247343;
RA Ohura T., Ogasawara M., Ikeda H., Narisawa K., Tada K.;
RT "The molecular defect in propionic acidemia: exon skipping caused by an 8-
RT bp deletion from an intron in the PCCB allele.";
RL Hum. Genet. 92:397-402(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PA-2.
RC TISSUE=Blood, and Skin fibroblast;
RX PubMed=9683601; DOI=10.1086/301970;
RA Rodriguez-Pombo P., Hoenicka J., Muro S., Perez B., Perez-Cerda C.,
RA Richard E., Desviat L.R., Ugarte M.;
RT "Human propionyl-CoA carboxylase beta subunit gene: exon-intron definition
RT and mutation spectrum in Spanish and Latin American propionic acidemia
RT patients.";
RL Am. J. Hum. Genet. 63:360-369(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Caudate nucleus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas, and Skin;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 289-443 (ISOFORM 1).
RX PubMed=3460076; DOI=10.1073/pnas.83.13.4864;
RA Lamhonwah A.-M., Barankiewicz T.J., Willard H.F., Mahuran D.J., Quan F.,
RA Gravel R.A.;
RT "Isolation of cDNA clones coding for the alpha and beta chains of human
RT propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms
RT associated with PCCA and PCCB genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:4864-4868(1986).
RN [9]
RP PROTEIN SEQUENCE OF 29-33, AND SUBCELLULAR LOCATION.
RC TISSUE=Kidney;
RX PubMed=16023992; DOI=10.1016/j.bbrc.2005.06.190;
RA Stadler S.C., Polanetz R., Meier S., Mayerhofer P.U., Herrmann J.M.,
RA Anslinger K., Roscher A.A., Roschinger W., Holzinger A.;
RT "Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-
RT CoA carboxylase.";
RL Biochem. Biophys. Res. Commun. 334:939-946(2005).
RN [10]
RP SEQUENCE REVISION.
RA Lamhonwah A.-M.;
RL Submitted (DEC-1986) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 401-433, AND VARIANT PA-2 ILE-408 DEL.
RC TISSUE=Skin fibroblast;
RX PubMed=2154743; DOI=10.1073/pnas.87.4.1372;
RA Tahara T., Kraus J.P., Rosenberg L.E.;
RT "An unusual insertion/deletion in the gene encoding the beta-subunit of
RT propionyl-CoA carboxylase is a frequent mutation in Caucasian propionic
RT acidemia.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:1372-1376(1990).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP SUBUNIT.
RX PubMed=6765947; DOI=10.1016/s0021-9258(19)86263-4;
RA Kalousek F., Darigo M.D., Rosenberg L.E.;
RT "Isolation and characterization of propionyl-CoA carboxylase from normal
RT human liver. Evidence for a protomeric tetramer of nonidentical subunits.";
RL J. Biol. Chem. 255:60-65(1980).
RN [13]
RP SUBUNIT.
RX PubMed=20725044; DOI=10.1038/nature09302;
RA Huang C.S., Sadre-Bazzaz K., Shen Y., Deng B., Zhou Z.H., Tong L.;
RT "Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme
RT A carboxylase.";
RL Nature 466:1001-1005(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-71, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP VARIANTS PA-2 TRP-410 AND ILE-408 DEL.
RX PubMed=8411997; DOI=10.1007/bf00710282;
RA Tahara T., Kraus J.P., Ohura T., Rosenberg L.E., Fenton W.A.;
RT "Three independent mutations in the same exon of the PCCB gene: differences
RT between Caucasian and Japanese propionic acidaemia.";
RL J. Inherit. Metab. Dis. 16:353-360(1993).
RN [17]
RP VARIANTS PA-2 MET-17; LYS-168; ASP-205 AND THR-442.
RX PubMed=10447268;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<89::aid-humu18>3.0.co;2-5;
RA Muro S., Rodriguez-Pombo P., Perez B., Perez-Cerda C., Desviat L.R.,
RA Sperl W., Skladal D., Sass J.O., Ugarte M.;
RT "Identification of novel mutations in the PCCB gene in European propionic
RT acidemia patients.";
RL Hum. Mutat. 14:89-90(1999).
RN [18]
RP REVIEW ON PA VARIANTS.
RX PubMed=10502773;
RX DOI=10.1002/(sici)1098-1004(199910)14:4<275::aid-humu1>3.0.co;2-n;
RA Ugarte M., Perez-Cerda C., Rodriguez-Pombo P., Desviat L.R., Perez B.,
RA Richard E., Muro S., Campeau E., Ohura T., Gravel R.A.;
RT "Overview of mutations in the PCCA and PCCB genes causing propionic
RT acidemia.";
RL Hum. Mutat. 14:275-282(1999).
RN [19]
RP CHARACTERIZATION OF VARIANTS PA-2 GLN-165; VAL-497; CYS-512; PRO-519 AND
RP ASP-536, AND CHARACTERIZATION OF VARIANT VAL-497.
RX PubMed=11749052; DOI=10.1006/mgme.2001.3254;
RA Muro S., Perez B., Desviat L.R., Rodriguez-Pombo P., Perez-Cerda C.,
RA Clavero S., Ugarte M.;
RT "Effect of PCCB gene mutations on the heteromeric and homomeric assembly of
RT propionyl-CoA carboxylase.";
RL Mol. Genet. Metab. 74:476-483(2001).
RN [20]
RP VARIANTS PA-2 ILE-428; LEU-430; CYS-435; CYS-439 AND THR-468.
RX PubMed=12189489; DOI=10.1007/s00439-002-0761-z;
RA Yorifuji T., Kawai M., Muroi J., Mamada M., Kurokawa K., Shigematsu Y.,
RA Hirano S., Sakura N., Yoshida I., Kuhara T., Endo F., Mitsubuchi H.,
RA Nakahata T.;
RT "Unexpectedly high prevalence of the mild form of propionic acidemia in
RT Japan: presence of a common mutation and possible clinical implications.";
RL Hum. Genet. 111:161-165(2002).
RN [21]
RP VARIANTS PA-2 SER-67; MET-107; ASP-112; GLN-165; LYS-168; ARG-188; VAL-246;
RP ILE-341 DEL AND TRP-410.
RX PubMed=12559849; DOI=10.1016/s1096-7192(02)00197-x;
RA Perez B., Desviat L.R., Rodriguez-Pombo P., Clavero S., Navarrete R.,
RA Perez-Cerda C., Ugarte M.;
RT "Propionic acidemia: identification of twenty-four novel mutations in
RT Europe and North America.";
RL Mol. Genet. Metab. 78:59-67(2003).
RN [22]
RP VARIANTS PA-2 PRO-153; TRP-165; TRP-410; ILE-428 AND CYS-512.
RX PubMed=15059621; DOI=10.1016/j.ymgme.2004.01.003;
RA Yang X., Sakamoto O., Matsubara Y., Kure S., Suzuki Y., Aoki Y.,
RA Yamaguchi S., Takahashi Y., Nishikubo T., Kawaguchi C., Yoshioka A.,
RA Kimura T., Hayasaka K., Kohno Y., Iinuma K., Ohura T.;
RT "Mutation spectrum of the PCCA and PCCB genes in Japanese patients with
RT propionic acidemia.";
RL Mol. Genet. Metab. 81:335-342(2004).
RN [23]
RP CHARACTERIZATION OF VARIANTS PA-2 TRP-165; LYS-168 AND TRP-410 AND CYS-512,
RP CHARACTERIZATION OF VARIANT VAL-497, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=15890657; DOI=10.1074/jbc.m413281200;
RA Jiang H., Rao K.S., Yee V.C., Kraus J.P.;
RT "Characterization of four variant forms of human propionyl-CoA carboxylase
RT expressed in Escherichia coli.";
RL J. Biol. Chem. 280:27719-27727(2005).
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:6765947, PubMed:15890657). Propionyl-CoA carboxylase catalyzes
CC the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-
CC CoA/(S)-methylmalonyl-CoA (PubMed:6765947, PubMed:15890657). Within the
CC holoenzyme, the alpha subunit catalyzes the ATP-dependent carboxylation
CC of the biotin carried by the biotin carboxyl carrier (BCC) domain,
CC while the beta subunit then transfers the carboxyl group from
CC carboxylated biotin to propionyl-CoA (By similarity). Propionyl-CoA
CC carboxylase also significantly acts on butyryl-CoA/butanoyl-CoA, which
CC is converted to ethylmalonyl-CoA/(2S)-ethylmalonyl-CoA at a much lower
CC rate (PubMed:6765947). Other alternative minor substrates include (2E)-
CC butenoyl-CoA/crotonoyl-CoA (By similarity).
CC {ECO:0000250|UniProtKB:P79384, ECO:0000250|UniProtKB:Q168G2,
CC ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}.
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:15890657, ECO:0000269|PubMed:6765947};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721;
CC Evidence={ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947};
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:P79384};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59521;
CC Evidence={ECO:0000250|UniProtKB:P79384};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.29 mM for propanoyl-CoA {ECO:0000269|PubMed:6765947};
CC KM=0.41 mM for propanoyl-CoA (at 37 degrees Celsius and pH 8.0)
CC {ECO:0000269|PubMed:15890657};
CC pH dependence:
CC Optimum pH is 7.2-8.8 for the propionyl-CoA carboxylase activity as
CC measured for the holoenzyme. {ECO:0000269|PubMed:6765947};
CC -!- PATHWAY: Metabolic intermediate metabolism; propanoyl-CoA degradation;
CC succinyl-CoA from propanoyl-CoA: step 1/3.
CC {ECO:0000269|PubMed:15890657, ECO:0000269|PubMed:6765947}.
CC -!- SUBUNIT: The holoenzyme is a dodecamer composed of 6 PCCA/alpha
CC subunits and 6 PCCB/beta subunits. {ECO:0000269|PubMed:20725044,
CC ECO:0000269|PubMed:6765947}.
CC -!- INTERACTION:
CC P05166; Q08043: ACTN3; NbExp=3; IntAct=EBI-1371908, EBI-2880652;
CC P05166; P05165: PCCA; NbExp=3; IntAct=EBI-1371908, EBI-2211679;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000305|PubMed:16023992}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P05166-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05166-2; Sequence=VSP_042568;
CC -!- DOMAIN: The beta subunit contains the carboxyl transferase (CT) domain.
CC {ECO:0000250|UniProtKB:Q168G2}.
CC -!- DISEASE: Propionic acidemia type II (PA-2) [MIM:606054]: Life-
CC threatening disease characterized by episodic vomiting, lethargy and
CC ketosis, neutropenia, periodic thrombocytopenia, hypogammaglobulinemia,
CC developmental retardation, and intolerance to protein.
CC {ECO:0000269|PubMed:10447268, ECO:0000269|PubMed:11749052,
CC ECO:0000269|PubMed:12189489, ECO:0000269|PubMed:12559849,
CC ECO:0000269|PubMed:15059621, ECO:0000269|PubMed:15890657,
CC ECO:0000269|PubMed:2154743, ECO:0000269|PubMed:8411997,
CC ECO:0000269|PubMed:9683601}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AccD/PCCB family. {ECO:0000305}.
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DR EMBL; X73424; CAA51825.1; -; mRNA.
DR EMBL; S67325; AAB28900.1; -; mRNA.
DR EMBL; AJ006487; CAA07066.1; -; Genomic_DNA.
DR EMBL; AJ006488; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006489; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006490; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006491; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006492; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006493; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006494; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006495; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006496; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006497; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006498; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AJ006499; CAA07066.1; JOINED; Genomic_DNA.
DR EMBL; AK295312; BAH12030.1; -; mRNA.
DR EMBL; AC069524; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79118.1; -; Genomic_DNA.
DR EMBL; BC013768; AAH13768.1; -; mRNA.
DR EMBL; BC053661; AAH53661.1; -; mRNA.
DR EMBL; M13573; AAA60036.1; -; mRNA.
DR EMBL; M31167; AAA60037.1; -; Genomic_DNA.
DR EMBL; M31169; AAA60038.1; -; Genomic_DNA.
DR CCDS; CCDS3089.1; -. [P05166-1]
DR CCDS; CCDS54643.1; -. [P05166-2]
DR PIR; T45009; T45009.
DR RefSeq; NP_000523.2; NM_000532.4. [P05166-1]
DR RefSeq; NP_001171485.1; NM_001178014.1. [P05166-2]
DR AlphaFoldDB; P05166; -.
DR SMR; P05166; -.
DR BioGRID; 111129; 143.
DR ComplexPortal; CPX-6169; Mitochondrial propionyl-CoA carboxylase complex.
DR CORUM; P05166; -.
DR DIP; DIP-38244N; -.
DR IntAct; P05166; 25.
DR MINT; P05166; -.
DR STRING; 9606.ENSP00000419027; -.
DR DrugBank; DB00121; Biotin.
DR DrugBank; DB00161; Valine.
DR iPTMnet; P05166; -.
DR PhosphoSitePlus; P05166; -.
DR BioMuta; PCCB; -.
DR DMDM; 124106304; -.
DR EPD; P05166; -.
DR jPOST; P05166; -.
DR MassIVE; P05166; -.
DR MaxQB; P05166; -.
DR PaxDb; P05166; -.
DR PeptideAtlas; P05166; -.
DR PRIDE; P05166; -.
DR ProteomicsDB; 51816; -. [P05166-1]
DR ProteomicsDB; 51817; -. [P05166-2]
DR Antibodypedia; 33408; 217 antibodies from 30 providers.
DR DNASU; 5096; -.
DR Ensembl; ENST00000251654.9; ENSP00000251654.4; ENSG00000114054.14. [P05166-1]
DR Ensembl; ENST00000469217.5; ENSP00000419027.1; ENSG00000114054.14. [P05166-2]
DR GeneID; 5096; -.
DR KEGG; hsa:5096; -.
DR MANE-Select; ENST00000251654.9; ENSP00000251654.4; NM_000532.5; NP_000523.2.
DR UCSC; uc003eqy.3; human. [P05166-1]
DR CTD; 5096; -.
DR DisGeNET; 5096; -.
DR GeneCards; PCCB; -.
DR GeneReviews; PCCB; -.
DR HGNC; HGNC:8654; PCCB.
DR HPA; ENSG00000114054; Tissue enhanced (liver).
DR MalaCards; PCCB; -.
DR MIM; 232050; gene.
DR MIM; 606054; phenotype.
DR neXtProt; NX_P05166; -.
DR OpenTargets; ENSG00000114054; -.
DR Orphanet; 35; Propionic acidemia.
DR PharmGKB; PA32993; -.
DR VEuPathDB; HostDB:ENSG00000114054; -.
DR eggNOG; KOG0540; Eukaryota.
DR GeneTree; ENSGT00940000157741; -.
DR InParanoid; P05166; -.
DR OMA; YAYAECT; -.
DR OrthoDB; 402617at2759; -.
DR PhylomeDB; P05166; -.
DR TreeFam; TF314350; -.
DR BioCyc; MetaCyc:ENSG00000114054-MON; -.
DR BRENDA; 6.4.1.3; 2681.
DR PathwayCommons; P05166; -.
DR Reactome; R-HSA-196780; Biotin transport and metabolism.
DR Reactome; R-HSA-3371599; Defective HLCS causes multiple carboxylase deficiency.
DR Reactome; R-HSA-71032; Propionyl-CoA catabolism.
DR SABIO-RK; P05166; -.
DR SignaLink; P05166; -.
DR SIGNOR; P05166; -.
DR UniPathway; UPA00945; UER00908.
DR BioGRID-ORCS; 5096; 11 hits in 1079 CRISPR screens.
DR ChiTaRS; PCCB; human.
DR GenomeRNAi; 5096; -.
DR Pharos; P05166; Tbio.
DR PRO; PR:P05166; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P05166; protein.
DR Bgee; ENSG00000114054; Expressed in right adrenal gland cortex and 203 other tissues.
DR ExpressionAtlas; P05166; baseline and differential.
DR Genevisible; P05166; HS.
DR GO; GO:1902494; C:catalytic complex; IPI:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004658; F:propionyl-CoA carboxylase activity; IDA:UniProtKB.
DR GO; GO:0009081; P:branched-chain amino acid metabolic process; IC:ComplexPortal.
DR GO; GO:0006631; P:fatty acid metabolic process; IC:ComplexPortal.
DR GO; GO:0019626; P:short-chain fatty acid catabolic process; IC:UniProtKB.
DR InterPro; IPR034733; AcCoA_carboxyl.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR011763; COA_CT_C.
DR InterPro; IPR011762; COA_CT_N.
DR Pfam; PF01039; Carboxyl_trans; 1.
DR SUPFAM; SSF52096; SSF52096; 2.
DR PROSITE; PS50989; COA_CT_CTER; 1.
DR PROSITE; PS50980; COA_CT_NTER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Disease variant; Ligase; Mitochondrion; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..28
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:16023992"
FT CHAIN 29..539
FT /note="Propionyl-CoA carboxylase beta chain, mitochondrial"
FT /id="PRO_0000000293"
FT DOMAIN 32..290
FT /note="CoA carboxyltransferase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136"
FT DOMAIN 294..533
FT /note="CoA carboxyltransferase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137"
FT REGION 32..533
FT /note="Carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01138"
FT REGION 325..358
FT /note="Acyl-CoA binding"
FT /evidence="ECO:0000255"
FT MOD_RES 71
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 99
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 99
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 248
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 474
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 474
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 489
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT MOD_RES 489
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MN9"
FT VAR_SEQ 124
FT /note="Q -> QQIIGWAQWLPLVISALWEAE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042568"
FT VARIANT 17
FT /note="L -> M (in PA-2; likely benign variant;
FT dbSNP:rs200185747)"
FT /evidence="ECO:0000269|PubMed:10447268"
FT /id="VAR_009080"
FT VARIANT 44
FT /note="R -> P (in PA-2)"
FT /id="VAR_000271"
FT VARIANT 67
FT /note="R -> S (in PA-2; dbSNP:rs747053913)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023847"
FT VARIANT 106
FT /note="S -> R (in PA-2)"
FT /id="VAR_000272"
FT VARIANT 107
FT /note="V -> M (in PA-2; dbSNP:rs1553774114)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023848"
FT VARIANT 112
FT /note="G -> D (in PA-2; dbSNP:rs202247818)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023849"
FT VARIANT 131
FT /note="G -> R (in PA-2)"
FT /id="VAR_000273"
FT VARIANT 140
FT /note="K -> KICK (in PA-2)"
FT /id="VAR_009081"
FT VARIANT 153
FT /note="A -> P (in PA-2; dbSNP:rs202247819)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_023850"
FT VARIANT 165
FT /note="R -> Q (in PA-2; does not affect either heteromeric
FT or homomeric assembly; dbSNP:rs1304714042)"
FT /evidence="ECO:0000269|PubMed:11749052,
FT ECO:0000269|PubMed:12559849"
FT /id="VAR_023851"
FT VARIANT 165
FT /note="R -> W (in PA-2; no effect on affinity for
FT propionyl-CoA; decreased reaction kinetics for the
FT propionyl-CoA carboxylase activity; decreased
FT thermostability affecting holoenzyme oligomerization;
FT dbSNP:rs879253815)"
FT /evidence="ECO:0000269|PubMed:15059621,
FT ECO:0000269|PubMed:15890657"
FT /id="VAR_000274"
FT VARIANT 168
FT /note="E -> K (in PA-2; no effect on affinity for
FT propionyl-CoA; decreased reaction kinetics for the
FT propionyl-CoA carboxylase activity; decreased
FT thermostability affecting holoenzyme oligomerization;
FT dbSNP:rs121964960)"
FT /evidence="ECO:0000269|PubMed:10447268,
FT ECO:0000269|PubMed:12559849, ECO:0000269|PubMed:15890657"
FT /id="VAR_000275"
FT VARIANT 188
FT /note="G -> R (in PA-2; dbSNP:rs746102997)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023852"
FT VARIANT 198
FT /note="G -> D (in PA-2; dbSNP:rs762354873)"
FT /id="VAR_000276"
FT VARIANT 205
FT /note="V -> D (in PA-2)"
FT /evidence="ECO:0000269|PubMed:10447268"
FT /id="VAR_009082"
FT VARIANT 228
FT /note="P -> L (in PA-2; dbSNP:rs374722096)"
FT /id="VAR_009083"
FT VARIANT 246
FT /note="G -> V (in PA-2)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023853"
FT VARIANT 287
FT /note="P -> S (in dbSNP:rs2228310)"
FT /evidence="ECO:0000269|PubMed:8188292"
FT /id="VAR_048163"
FT VARIANT 341
FT /note="Missing (in PA-2)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023854"
FT VARIANT 408
FT /note="Missing (in PA-2)"
FT /evidence="ECO:0000269|PubMed:2154743,
FT ECO:0000269|PubMed:8411997"
FT /id="VAR_000277"
FT VARIANT 410
FT /note="R -> W (in PA-2; no effect on affinity for
FT propionyl-CoA; decreased reaction kinetics for the
FT propionyl-CoA carboxylase activity; decreased
FT thermostability affecting holoenzyme oligomerization;
FT dbSNP:rs121964959)"
FT /evidence="ECO:0000269|PubMed:12559849,
FT ECO:0000269|PubMed:15059621, ECO:0000269|PubMed:15890657,
FT ECO:0000269|PubMed:8411997"
FT /id="VAR_000278"
FT VARIANT 428
FT /note="T -> I (in PA-2; dbSNP:rs111033542)"
FT /evidence="ECO:0000269|PubMed:12189489,
FT ECO:0000269|PubMed:15059621"
FT /id="VAR_009084"
FT VARIANT 430
FT /note="I -> L (in PA-2)"
FT /evidence="ECO:0000269|PubMed:12189489"
FT /id="VAR_023855"
FT VARIANT 435
FT /note="Y -> C (in PA-2; dbSNP:rs121964961)"
FT /evidence="ECO:0000269|PubMed:12189489"
FT /id="VAR_023856"
FT VARIANT 439
FT /note="Y -> C (in PA-2; dbSNP:rs769521436)"
FT /evidence="ECO:0000269|PubMed:12189489"
FT /id="VAR_023857"
FT VARIANT 442
FT /note="M -> T (in PA-2)"
FT /evidence="ECO:0000269|PubMed:10447268"
FT /id="VAR_009085"
FT VARIANT 468
FT /note="A -> T (in PA-2; dbSNP:rs775563122)"
FT /evidence="ECO:0000269|PubMed:12189489"
FT /id="VAR_023858"
FT VARIANT 497
FT /note="A -> V (found in patients with propionic acidemia;
FT does not affect either heteromeric or homomeric assembly;
FT decreased thermostability affecting holoenzyme
FT oligomerization; no effect on propionyl-CoA carboxylase
FT activity; dbSNP:rs142403318)"
FT /evidence="ECO:0000269|PubMed:11749052"
FT /id="VAR_000279"
FT VARIANT 512
FT /note="R -> C (in PA-2; affects heteromeric and homomeric
FT assembly; dbSNP:rs186710233)"
FT /evidence="ECO:0000269|PubMed:11749052,
FT ECO:0000269|PubMed:15059621"
FT /id="VAR_000280"
FT VARIANT 519
FT /note="L -> P (in PA-2; affects heteromeric and homomeric
FT assembly; dbSNP:rs202247822)"
FT /evidence="ECO:0000269|PubMed:11749052"
FT /id="VAR_000281"
FT VARIANT 536
FT /note="N -> D (in PA-2; affects heteromeric and homomeric
FT assembly; dbSNP:rs202247823)"
FT /evidence="ECO:0000269|PubMed:11749052"
FT /id="VAR_009086"
FT CONFLICT 58..59
FT /note="QH -> HD (in Ref. 2; AAB28900)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 539 AA; 58216 MW; A2DAAC00312D3C0F CRC64;
MAAALRVAAV GARLSVLASG LRAAVRSLCS QATSVNERIE NKRRTALLGG GQRRIDAQHK
RGKLTARERI SLLLDPGSFV ESDMFVEHRC ADFGMAADKN KFPGDSVVTG RGRINGRLVY
VFSQDFTVFG GSLSGAHAQK ICKIMDQAIT VGAPVIGLND SGGARIQEGV ESLAGYADIF
LRNVTASGVI PQISLIMGPC AGGAVYSPAL TDFTFMVKDT SYLFITGPDV VKSVTNEDVT
QEELGGAKTH TTMSGVAHRA FENDVDALCN LRDFFNYLPL SSQDPAPVRE CHDPSDRLVP
ELDTIVPLES TKAYNMVDII HSVVDEREFF EIMPNYAKNI IVGFARMNGR TVGIVGNQPK
VASGCLDINS SVKGARFVRF CDAFNIPLIT FVDVPGFLPG TAQEYGGIIR HGAKLLYAFA
EATVPKVTVI TRKAYGGAYD VMSSKHLCGD TNYAWPTAEI AVMGAKGAVE IIFKGHENVE
AAQAEYIEKF ANPFPAAVRG FVDDIIQPSS TRARICCDLD VLASKKVQRP WRKHANIPL
