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 27-MAR-2024, entry version 248. 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00409}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|PROSITE- CC 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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU01066, ECO:0000269|PubMed:6765947}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.08 mM for ATP {ECO:0000269|PubMed:6765947}; CC KM=3 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 7YBU; EM; 2.20 A; A/B/D/F/H/J=1-728. DR PDBsum; 2CQY; -. DR PDBsum; 2JKU; -. DR PDBsum; 7YBU; -. DR AlphaFoldDB; P05165; -. DR EMDB; EMD-33729; -. DR SMR; P05165; -. DR BioGRID; 111128; 147. DR ComplexPortal; CPX-6169; Mitochondrial propionyl-CoA carboxylase complex. DR CORUM; P05165; -. DR DIP; DIP-57493N; -. DR IntAct; P05165; 37. DR MINT; P05165; -. DR STRING; 9606.ENSP00000365462; -. DR DrugBank; DB00121; Biotin. DR GlyGen; P05165; 2 sites, 1 O-linked glycan (2 sites). 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; 9606-ENSP00000365462; -. DR PeptideAtlas; P05165; -. DR ProteomicsDB; 11147; -. DR ProteomicsDB; 51814; -. [P05165-1] DR ProteomicsDB; 51815; -. [P05165-2] DR Pumba; P05165; -. DR Antibodypedia; 25211; 223 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 AGR; HGNC:8653; -. 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; IGPKHYS; -. DR OrthoDB; 1129179at2759; -. DR PhylomeDB; P05165; -. DR TreeFam; TF354220; -. DR BioCyc; MetaCyc:ENSG00000175198-MONOMER; -. 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; 14 hits in 1151 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 200 other cell types or tissues. DR ExpressionAtlas; P05165; baseline and differential. 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; NAS:ComplexPortal. DR GO; GO:0006631; P:fatty acid metabolic process; NAS:ComplexPortal. DR GO; GO:0019626; P:short-chain fatty acid catabolic process; IC:UniProtKB. DR CDD; cd06850; biotinyl_domain; 1. DR Gene3D; 2.40.50.100; -; 1. DR Gene3D; 3.30.700.30; -; 1. DR Gene3D; 3.40.50.20; -; 1. DR Gene3D; 3.30.1490.20; ATP-grasp fold, A domain; 1. DR Gene3D; 3.30.470.20; ATP-grasp fold, B domain; 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 PANTHER; PTHR18866; CARBOXYLASE:PYRUVATE/ACETYL-COA/PROPIONYL-COA CARBOXYLASE; 1. DR PANTHER; PTHR18866:SF33; METHYLCROTONOYL-COA CARBOXYLASE SUBUNIT ALPHA, MITOCHONDRIAL-RELATED; 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; PF18140; PCC_BT; 1. DR SMART; SM00878; Biotin_carb_C; 1. DR SUPFAM; SSF56059; Glutathione synthetase ATP-binding 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; PS00866; CPSASE_1; 1. DR PROSITE; PS00867; CPSASE_2; 1. DR Genevisible; P05165; HS. 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 //