PCCA_HUMAN
ID PCCA_HUMAN Reviewed; 728 AA.
AC P05165; B4DKY8; B4DPF9; C9JPQ8; Q15979; Q8WXQ7;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 4.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Propionyl-CoA carboxylase alpha chain, mitochondrial {ECO:0000305|PubMed:2740237};
DE Short=PCCase subunit alpha;
DE EC=6.4.1.3 {ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582};
DE AltName: Full=Propanoyl-CoA:carbon dioxide ligase subunit alpha;
DE Flags: Precursor;
GN Name=PCCA {ECO:0000312|HGNC:HGNC:8653};
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RX PubMed=11592820; DOI=10.1006/mgme.2001.3210;
RA Campeau E., Desviat L.R., Leclerc D., Wu X., Perez B., Ugarte M.,
RA Gravel R.A.;
RT "Structure of the PCCA gene and distribution of mutations causing propionic
RT acidemia.";
RL Mol. Genet. Metab. 74:238-247(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Kidney, and Tongue;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-728 (ISOFORM 1).
RC TISSUE=Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-728 (ISOFORM 1).
RX PubMed=2740237; DOI=10.1093/nar/17.11.4396;
RA Lamhonwah A.-M., Mahuran D.J., Gravel R.A.;
RT "Human mitochondrial propionyl-CoA carboxylase: localization of the N-
RT terminus of the pro- and mature alpha chains in the deduced primary
RT sequence of a full-length cDNA.";
RL Nucleic Acids Res. 17:4396-4396(1989).
RN [7]
RP SEQUENCE REVISION.
RA Gravel R.A.;
RL Submitted (APR-1993) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PROTEIN SEQUENCE OF 53-58, 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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 364-392, FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC TISSUE=Liver;
RX PubMed=8434582;
RA Stankovics J., Ledley F.D.;
RT "Cloning of functional alpha propionyl CoA carboxylase and correction of
RT enzyme deficiency in pccA fibroblasts.";
RL Am. J. Hum. Genet. 52:144-151(1993).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 369-561.
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 [11]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 633-728.
RX PubMed=3555348; DOI=10.1016/0003-9861(87)90146-9;
RA Lamhonwah A.-M., Quan F., Gravel R.A.;
RT "Sequence homology around the biotin-binding site of human propionyl-CoA
RT carboxylase and pyruvate carboxylase.";
RL Arch. Biochem. Biophys. 254:631-636(1987).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND 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 BIOTINYLATION BY HLCS.
RX PubMed=7753853; DOI=10.1073/pnas.92.10.4626;
RA Leon-Del-Rio A., Leclerc D., Akerman B., Wakamatsu N., Gravel R.A.;
RT "Isolation of a cDNA encoding human holocarboxylase synthetase by
RT functional complementation of a biotin auxotroph of Escherichia coli.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:4626-4630(1995).
RN [14]
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 [15]
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 [16]
RP INTERACTION WITH SIRT4; SIRT3 AND SIRT5.
RX PubMed=23438705; DOI=10.1016/j.mito.2013.02.002;
RA Wirth M., Karaca S., Wenzel D., Ho L., Tishkoff D., Lombard D.B.,
RA Verdin E., Urlaub H., Jedrusik-Bode M., Fischle W.;
RT "Mitochondrial SIRT4-type proteins in Caenorhabditis elegans and mammals
RT interact with pyruvate carboxylase and other acetylated biotin-dependent
RT carboxylases.";
RL Mitochondrion 13:705-720(2013).
RN [17]
RP IDENTIFICATION BY 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 [18]
RP STRUCTURE BY NMR OF 175-270.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of B domain from human propionyl-CoA carboxylase alpha
RT subunit.";
RL Submitted (NOV-2005) to the PDB data bank.
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 658-728, AND BIOTINYLATION AT
RP LYS-694 BY HLCS.
RX PubMed=20443544; DOI=10.1021/bi901612y;
RA Healy S., McDonald M.K., Wu X., Yue W.W., Kochan G., Oppermann U.,
RA Gravel R.A.;
RT "Structural impact of human and Escherichia coli biotin carboxyl carrier
RT proteins on biotin attachment.";
RL Biochemistry 49:4687-4694(2010).
RN [20]
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 [21]
RP VARIANTS PA-1 TRP-77; THR-138; THR-164; LYS-373 AND ARG-631,
RP CHARACTERIZATION OF VARIANTS PA-1 TRP-77; THR-138; THR-164; LYS-373 AND
RP ARG-631, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10101253; DOI=10.1016/s0925-4439(99)00008-3;
RA Richard E., Desviat L.R., Perez B., Perez-Cerda C., Ugarte M.;
RT "Genetic heterogeneity in propionic acidemia patients with alpha-subunit
RT defects: identification of five novel mutations, one of them causing
RT instability of the protein.";
RL Biochim. Biophys. Acta 1453:351-358(1999).
RN [22]
RP VARIANT PHE-551, AND VARIANT PA-1 LEU-532 DEL.
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 [23]
RP VARIANTS PA-1 TRP-77; GLU-197; ARG-297; ARG-398; GLN-399; LEU-423 AND
RP LEU-559.
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 [24]
RP VARIANTS PA-1 PRO-75; LYS-229; GLY-368; VAL-379; ARG-668 AND CYS-712 DEL,
RP CHARACTERIZATION OF VARIANTS PA-1 ARG-668 AND CYS-712 DEL, DOMAIN, AND
RP BIOTINYLATION.
RX PubMed=10329019; DOI=10.1006/mgme.1999.2850;
RA Campeau E., Dupuis L., Leon-Del-Rio A., Gravel R.;
RT "Coding sequence mutations in the alpha subunit of propionyl-CoA
RT carboxylase in patients with propionic acidemia.";
RL Mol. Genet. Metab. 67:11-22(1999).
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:8434582, PubMed:6765947). Propionyl-CoA carboxylase catalyzes
CC the carboxylation of propionyl-CoA/propanoyl-CoA to D-methylmalonyl-
CC CoA/(S)-methylmalonyl-CoA (PubMed:8434582, PubMed:6765947,
CC PubMed:10101253). Within the holoenzyme, the alpha subunit catalyzes
CC the 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 at a much lower rate (PubMed:6765947). Other
CC alternative minor substrates include (2E)-butenoyl-CoA/crotonoyl-CoA
CC (By similarity). {ECO:0000250|UniProtKB:P0DTA4,
CC ECO:0000250|UniProtKB:Q5LUF3, ECO:0000269|PubMed:10101253,
CC ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582}.
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; Evidence={ECO:0000269|PubMed:6765947,
CC ECO:0000269|PubMed:8434582};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23721;
CC Evidence={ECO:0000269|PubMed:6765947, ECO:0000269|PubMed:8434582};
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=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:6765947};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.08 mM for ATP {ECO:0000269|PubMed:6765947};
CC KM=3.0 mM for hydrogencarbonate {ECO:0000269|PubMed:6765947};
CC pH dependence:
CC Optimum pH is 7.2-8.8 for the propionyl-CoA carboxylase activity
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. {ECO:0000269|PubMed:6765947,
CC ECO:0000269|PubMed:8434582}.
CC -!- SUBUNIT: The holoenzyme is a dodecamer composed of 6 PCCA/alpha
CC subunits and 6 PCCB/beta subunits (PubMed:6765947, PubMed:20725044).
CC Interacts (via the biotin carboxylation domain) with SIRT4
CC (PubMed:23438705). Interacts with SIRT3 and SIRT5 (PubMed:23438705).
CC {ECO:0000269|PubMed:20725044, ECO:0000269|PubMed:23438705,
CC ECO:0000269|PubMed:6765947, ECO:0000305}.
CC -!- INTERACTION:
CC P05165; P23508: MCC; NbExp=3; IntAct=EBI-2211679, EBI-307531;
CC P05165; P05166: PCCB; NbExp=3; IntAct=EBI-2211679, EBI-1371908;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:10101253, ECO:0000269|PubMed:16023992}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P05165-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05165-2; Sequence=VSP_039857;
CC Name=3;
CC IsoId=P05165-3; Sequence=VSP_044458;
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:0000305|PubMed:10329019}.
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 (PubMed:10329019). Biotinylation is catalyzed by HLCS (PubMed:7753853,
CC PubMed:20443544). {ECO:0000269|PubMed:10329019,
CC ECO:0000269|PubMed:20443544, ECO:0000269|PubMed:7753853}.
CC -!- DISEASE: Propionic acidemia type I (PA-1) [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:10101253, ECO:0000269|PubMed:10329019,
CC ECO:0000269|PubMed:12559849, ECO:0000269|PubMed:15059621}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA60035.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH00140.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAK61392.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA32763.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF385926; AAL66189.1; -; mRNA.
DR EMBL; AY035808; AAK61392.1; ALT_INIT; Genomic_DNA.
DR EMBL; AY035786; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035787; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035788; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035789; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035790; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035791; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035792; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035793; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035794; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035795; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035796; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035797; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035798; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035799; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035800; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035801; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035802; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035803; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035804; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035805; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035806; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AY035807; AAK61392.1; JOINED; Genomic_DNA.
DR EMBL; AK296771; BAG59350.1; -; mRNA.
DR EMBL; AK298318; BAG60571.1; -; mRNA.
DR EMBL; AL355338; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356575; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136526; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353697; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471085; EAX09034.1; -; Genomic_DNA.
DR EMBL; BC000140; AAH00140.1; ALT_INIT; mRNA.
DR EMBL; X14608; CAA32763.1; ALT_FRAME; mRNA.
DR EMBL; S55656; AAB25345.1; -; mRNA.
DR EMBL; M13572; AAA60035.1; ALT_FRAME; mRNA.
DR EMBL; M26121; AAA36424.1; -; mRNA.
DR CCDS; CCDS45065.1; -. [P05165-2]
DR CCDS; CCDS53878.1; -. [P05165-3]
DR CCDS; CCDS9496.2; -. [P05165-1]
DR PIR; S04613; A27883.
DR RefSeq; NP_000273.2; NM_000282.3. [P05165-1]
DR RefSeq; NP_001121164.1; NM_001127692.2. [P05165-2]
DR RefSeq; NP_001171475.1; NM_001178004.1. [P05165-3]
DR PDB; 2CQY; NMR; -; A=176-270.
DR PDB; 2JKU; X-ray; 1.50 A; A=658-728.
DR PDBsum; 2CQY; -.
DR PDBsum; 2JKU; -.
DR AlphaFoldDB; P05165; -.
DR SMR; P05165; -.
DR BioGRID; 111128; 107.
DR ComplexPortal; CPX-6169; Mitochondrial propionyl-CoA carboxylase complex.
DR CORUM; P05165; -.
DR DIP; DIP-57493N; -.
DR IntAct; P05165; 31.
DR MINT; P05165; -.
DR STRING; 9606.ENSP00000365462; -.
DR DrugBank; DB00121; Biotin.
DR GlyGen; P05165; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P05165; -.
DR PhosphoSitePlus; P05165; -.
DR SwissPalm; P05165; -.
DR BioMuta; PCCA; -.
DR DMDM; 308153661; -.
DR EPD; P05165; -.
DR jPOST; P05165; -.
DR MassIVE; P05165; -.
DR MaxQB; P05165; -.
DR PaxDb; P05165; -.
DR PeptideAtlas; P05165; -.
DR PRIDE; P05165; -.
DR ProteomicsDB; 11147; -.
DR ProteomicsDB; 51814; -. [P05165-1]
DR ProteomicsDB; 51815; -. [P05165-2]
DR Antibodypedia; 25211; 202 antibodies from 27 providers.
DR DNASU; 5095; -.
DR Ensembl; ENST00000376279.7; ENSP00000365456.3; ENSG00000175198.17. [P05165-3]
DR Ensembl; ENST00000376285.6; ENSP00000365462.1; ENSG00000175198.17. [P05165-1]
DR Ensembl; ENST00000376286.8; ENSP00000365463.4; ENSG00000175198.17. [P05165-2]
DR GeneID; 5095; -.
DR KEGG; hsa:5095; -.
DR MANE-Select; ENST00000376285.6; ENSP00000365462.1; NM_000282.4; NP_000273.2.
DR UCSC; uc001voo.4; human. [P05165-1]
DR CTD; 5095; -.
DR DisGeNET; 5095; -.
DR GeneCards; PCCA; -.
DR GeneReviews; PCCA; -.
DR HGNC; HGNC:8653; PCCA.
DR HPA; ENSG00000175198; Tissue enhanced (epididymis).
DR MalaCards; PCCA; -.
DR MIM; 232000; gene.
DR MIM; 606054; phenotype.
DR neXtProt; NX_P05165; -.
DR OpenTargets; ENSG00000175198; -.
DR Orphanet; 35; Propionic acidemia.
DR PharmGKB; PA32992; -.
DR VEuPathDB; HostDB:ENSG00000175198; -.
DR eggNOG; KOG0238; Eukaryota.
DR GeneTree; ENSGT00940000156083; -.
DR HOGENOM; CLU_000395_3_3_1; -.
DR InParanoid; P05165; -.
DR OMA; ITHFHTP; -.
DR OrthoDB; 254436at2759; -.
DR PhylomeDB; P05165; -.
DR TreeFam; TF354220; -.
DR BioCyc; MetaCyc:ENSG00000175198-MON; -.
DR BRENDA; 6.4.1.3; 2681.
DR PathwayCommons; P05165; -.
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; P05165; -.
DR SignaLink; P05165; -.
DR SIGNOR; P05165; -.
DR UniPathway; UPA00945; UER00908.
DR BioGRID-ORCS; 5095; 12 hits in 1071 CRISPR screens.
DR ChiTaRS; PCCA; human.
DR EvolutionaryTrace; P05165; -.
DR GenomeRNAi; 5095; -.
DR Pharos; P05165; Tbio.
DR PRO; PR:P05165; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P05165; protein.
DR Bgee; ENSG00000175198; Expressed in right lobe of liver and 198 other tissues.
DR ExpressionAtlas; P05165; baseline and differential.
DR Genevisible; P05165; 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; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009374; F:biotin binding; TAS:ProtInc.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
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: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 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 3D-structure; Acetylation; Alternative splicing; ATP-binding; Biotin;
KW Direct protein sequencing; Disease variant; 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:0000269|PubMed:16023992"
FT CHAIN 53..728
FT /note="Propionyl-CoA carboxylase alpha chain,
FT mitochondrial"
FT /id="PRO_0000002837"
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 653..728
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 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 328
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 328
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 385
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 496
FT /note="N6-acetyllysine"
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 648
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZA3"
FT MOD_RES 694
FT /note="N6-biotinyllysine; by HLCS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066,
FT ECO:0000269|PubMed:20443544"
FT VAR_SEQ 36..61
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039857"
FT VAR_SEQ 634..680
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044458"
FT VARIANT 75
FT /note="A -> P (in PA-1; dbSNP:rs794727479)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009087"
FT VARIANT 77
FT /note="R -> W (in PA-1; loss of function;
FT dbSNP:rs141371306)"
FT /evidence="ECO:0000269|PubMed:10101253,
FT ECO:0000269|PubMed:15059621"
FT /id="VAR_009088"
FT VARIANT 138
FT /note="A -> T (in PA-1; loss of function;
FT dbSNP:rs202247814)"
FT /evidence="ECO:0000269|PubMed:10101253"
FT /id="VAR_009089"
FT VARIANT 164
FT /note="I -> T (in PA-1; loss of function;
FT dbSNP:rs202247815)"
FT /evidence="ECO:0000269|PubMed:10101253"
FT /id="VAR_009090"
FT VARIANT 197
FT /note="G -> E (in PA-1)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_023843"
FT VARIANT 229
FT /note="M -> K (in PA-1; dbSNP:rs375628794)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009091"
FT VARIANT 297
FT /note="Q -> R (in PA-1)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_009092"
FT VARIANT 368
FT /note="D -> G (in PA-1)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009093"
FT VARIANT 373
FT /note="M -> K (in PA-1; unstable protein; loss of function;
FT dbSNP:rs121964958)"
FT /evidence="ECO:0000269|PubMed:10101253"
FT /id="VAR_009094"
FT VARIANT 379
FT /note="G -> V (in PA-1; dbSNP:rs794727087)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009095"
FT VARIANT 398
FT /note="C -> R (in PA-1)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_023844"
FT VARIANT 399
FT /note="R -> Q (in PA-1; dbSNP:rs1301904623)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_009096"
FT VARIANT 423
FT /note="P -> L (in PA-1; dbSNP:rs1443858896)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_009097"
FT VARIANT 475
FT /note="I -> V (in dbSNP:rs35719359)"
FT /id="VAR_009098"
FT VARIANT 532
FT /note="Missing (in PA-1)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023845"
FT VARIANT 551
FT /note="V -> F (in dbSNP:rs61749895)"
FT /evidence="ECO:0000269|PubMed:12559849"
FT /id="VAR_023846"
FT VARIANT 559
FT /note="W -> L (in PA-1; dbSNP:rs118169528)"
FT /evidence="ECO:0000269|PubMed:15059621"
FT /id="VAR_009099"
FT VARIANT 631
FT /note="G -> R (in PA-1; loss of function;
FT dbSNP:rs796052018)"
FT /evidence="ECO:0000269|PubMed:10101253"
FT /id="VAR_009100"
FT VARIANT 668
FT /note="G -> R (in PA-1; loss of biotinylation;
FT dbSNP:rs771438170)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009101"
FT VARIANT 712
FT /note="Missing (in PA-1; loss of biotinylation)"
FT /evidence="ECO:0000269|PubMed:10329019"
FT /id="VAR_009102"
FT CONFLICT 61
FT /note="K -> E (in Ref. 2; BAG60571)"
FT /evidence="ECO:0000305"
FT CONFLICT 93
FT /note="H -> Y (in Ref. 4; BAG59350)"
FT /evidence="ECO:0000305"
FT CONFLICT 373
FT /note="M -> R (in Ref. 10; AAA60035)"
FT /evidence="ECO:0000305"
FT CONFLICT 378..379
FT /note="KG -> RS (in Ref. 10; AAA60035)"
FT /evidence="ECO:0000305"
FT CONFLICT 558
FT /note="N -> H (in Ref. 10; AAA60035)"
FT /evidence="ECO:0000305"
FT CONFLICT 610
FT /note="T -> A (in Ref. 4; BAG59350)"
FT /evidence="ECO:0000305"
FT CONFLICT 679
FT /note="D -> A (in Ref. 11; AAA36424)"
FT /evidence="ECO:0000305"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:2CQY"
FT HELIX 202..212
FT /evidence="ECO:0007829|PDB:2CQY"
FT STRAND 214..220
FT /evidence="ECO:0007829|PDB:2CQY"
FT TURN 226..228
FT /evidence="ECO:0007829|PDB:2CQY"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:2CQY"
FT HELIX 235..252
FT /evidence="ECO:0007829|PDB:2CQY"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:2CQY"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:2CQY"
FT STRAND 665..667
FT /evidence="ECO:0007829|PDB:2JKU"
FT STRAND 669..673
FT /evidence="ECO:0007829|PDB:2JKU"
FT STRAND 688..691
FT /evidence="ECO:0007829|PDB:2JKU"
SQ SEQUENCE 728 AA; 80059 MW; 065F64186A0B8CCC CRC64;
MAGFWVGTAP LVAAGRRGRW PPQQLMLSAA LRTLKHVLYY SRQCLMVSRN LGSVGYDPNE
KTFDKILVAN RGEIACRVIR TCKKMGIKTV AIHSDVDASS VHVKMADEAV CVGPAPTSKS
YLNMDAIMEA IKKTRAQAVH PGYGFLSENK EFARCLAAED VVFIGPDTHA IQAMGDKIES
KLLAKKAEVN TIPGFDGVVK DAEEAVRIAR EIGYPVMIKA SAGGGGKGMR IAWDDEETRD
GFRLSSQEAA SSFGDDRLLI EKFIDNPRHI EIQVLGDKHG NALWLNEREC SIQRRNQKVV
EEAPSIFLDA ETRRAMGEQA VALARAVKYS SAGTVEFLVD SKKNFYFLEM NTRLQVEHPV
TECITGLDLV QEMIRVAKGY PLRHKQADIR INGWAVECRV YAEDPYKSFG LPSIGRLSQY
QEPLHLPGVR VDSGIQPGSD ISIYYDPMIS KLITYGSDRT EALKRMADAL DNYVIRGVTH
NIALLREVII NSRFVKGDIS TKFLSDVYPD GFKGHMLTKS EKNQLLAIAS SLFVAFQLRA
QHFQENSRMP VIKPDIANWE LSVKLHDKVH TVVASNNGSV FSVEVDGSKL NVTSTWNLAS
PLLSVSVDGT QRTVQCLSRE AGGNMSIQFL GTVYKVNILT RLAAELNKFM LEKVTEDTSS
VLRSPMPGVV VAVSVKPGDA VAEGQEICVI EAMKMQNSMT AGKTGTVKSV HCQAGDTVGE
GDLLVELE
