MCCA_HUMAN
ID MCCA_HUMAN Reviewed; 725 AA.
AC Q96RQ3; Q59ES4; Q9H959; Q9NS97;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 3.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Methylcrotonoyl-CoA carboxylase subunit alpha, mitochondrial;
DE Short=MCCase subunit alpha;
DE EC=6.4.1.4;
DE AltName: Full=3-methylcrotonyl-CoA carboxylase 1;
DE AltName: Full=3-methylcrotonyl-CoA carboxylase biotin-containing subunit;
DE AltName: Full=3-methylcrotonyl-CoA:carbon dioxide ligase subunit alpha;
DE Flags: Precursor;
GN Name=MCCC1; Synonyms=MCCA;
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], INVOLVEMENT IN MCC1D, AND VARIANTS MCC1D
RP ARG-325 AND SER-385.
RX PubMed=11170888; DOI=10.1086/318202;
RA Gallardo M.E., Desviat L.R., Rodriguez J.M., Esparza-Gordillo J.,
RA Perez-Cerda C., Perez B., Rodriguez-Pombo P., Criado O., Sanz R.,
RA Morton D.H., Gibson K.M., Le T.P., Ribes A., Rodriguez de Cordoba S.,
RA Ugarte M., Penalva M.A.;
RT "The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine
RT catabolism.";
RL Am. J. Hum. Genet. 68:334-346(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11401427; DOI=10.1006/geno.2000.6366;
RA Obata K., Fukuda T., Morishita R., Abe S., Asakawa S., Yamaguchi S.,
RA Yoshino M., Ihara K., Murayama K., Shigemoto K., Shimizu N., Kondo I.;
RT "Human biotin-containing subunit of 3-methylcrotonyl-CoA carboxylase gene
RT (MCCA): cDNA sequence, genomic organization, localization to chromosomal
RT band 3q27, and expression.";
RL Genomics 72:145-152(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT MCC1D PHE-535, AND VARIANT PRO-464.
RX PubMed=11406611; DOI=10.1093/hmg/10.12.1299;
RA Holzinger A., Roeschinger W., Lagler F., Mayerhofer P.U., Lichtner P.,
RA Kattenfeld T., Thuy L.P., Nyhan W.L., Koch H.G., Muntau A.C., Roscher A.A.;
RT "Cloning of the human MCCA and MCCB genes and mutations therein reveal the
RT molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency.";
RL Hum. Mol. Genet. 10:1299-1306(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS MCC1D VAL-289; SER-385; PRO-437 AND
RP HIS-532, AND VARIANT PRO-464.
RX PubMed=11181649; DOI=10.1172/jci11948;
RA Baumgartner M.R., Almashanu S., Suormala T., Obie C., Cole R.N.,
RA Packman S., Baumgartner E.R., Valle D.;
RT "The molecular basis of human 3-methylcrotonyl-CoA carboxylase
RT deficiency.";
RL J. Clin. Invest. 107:495-504(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-464.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT MCC1D TRP-232, AND VARIANT
RP PRO-464.
RC TISSUE=Aorta;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-464.
RC TISSUE=Skeletal muscle;
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 PROTEIN SEQUENCE OF 42-47, 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 FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=17360195; DOI=10.1016/j.pep.2007.01.012;
RA Chu C.H., Cheng D.;
RT "Expression, purification, characterization of human 3-methylcrotonyl-CoA
RT carboxylase (MCCC).";
RL Protein Expr. Purif. 53:421-427(2007).
RN [10]
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 [11]
RP INTERACTION WITH SIRT4.
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 [12]
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [14]
RP STRUCTURE BY NMR OF 640-725.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of RSGI RUH-072, an apo-biotinyl domain from human
RT acetyl coenzyme A carboxylase.";
RL Submitted (SEP-2007) to the PDB data bank.
RN [15]
RP VARIANTS MCC1D LYS-134; PRO-187; TRP-232; VAL-291 AND SER-385, AND
RP CHARACTERIZATION OF VARIANT MCC1D VAL-291.
RX PubMed=16010683; DOI=10.1002/humu.9352;
RA Dantas M.F., Suormala T., Randolph A., Coelho D., Fowler B., Valle D.,
RA Baumgartner M.R.;
RT "3-Methylcrotonyl-CoA carboxylase deficiency: mutation analysis in 28
RT probands, 9 symptomatic and 19 detected by newborn screening.";
RL Hum. Mutat. 26:164-174(2005).
RN [16]
RP VARIANT MCC1D MET-460.
RX PubMed=17968484; DOI=10.1007/s10038-007-0211-9;
RA Uematsu M., Sakamoto O., Sugawara N., Kumagai N., Morimoto T.,
RA Yamaguchi S., Hasegawa Y., Kobayashi H., Ihara K., Yoshino M., Watanabe Y.,
RA Inokuchi T., Yokoyama T., Kiwaki K., Nakamura K., Endo F., Tsuchiya S.,
RA Ohura T.;
RT "Novel mutations in five Japanese patients with 3-methylcrotonyl-CoA
RT carboxylase deficiency.";
RL J. Hum. Genet. 52:1040-1043(2007).
RN [17]
RP VARIANT MCC1D GLU-46.
RX PubMed=21071250; DOI=10.1016/j.ymgme.2010.10.008;
RA Nguyen K.V., Naviaux R.K., Patra S., Barshop B.A., Nyhan W.L.;
RT "Novel mutations in the human MCCA and MCCB gene causing
RT methylcrotonylglycinuria.";
RL Mol. Genet. Metab. 102:218-221(2011).
RN [18]
RP VARIANTS MCC1D ARG-276 AND GLN-281.
RX PubMed=22150417; DOI=10.1111/j.1399-0004.2011.01704.x;
RA Cho S.Y., Park H.D., Lee Y.W., Ki C.S., Lee S.Y., Sohn Y.B., Park S.W.,
RA Kim S.H., Ji S., Kim S.J., Choi E.W., Kim C.H., Ko A.R., Paik K.H.,
RA Lee D.H., Jin D.K.;
RT "Mutational spectrum in eight Korean patients with 3-methylcrotonyl-CoA
RT carboxylase deficiency.";
RL Clin. Genet. 81:96-98(2012).
RN [19]
RP VARIANTS MCC1D LYS-56; GLN-281; PRO-380 AND SER-385.
RX PubMed=22264772; DOI=10.1016/j.ymgme.2011.12.018;
RA Morscher R.J., Grunert S.C., Burer C., Burda P., Suormala T., Fowler B.,
RA Baumgartner M.R.;
RT "A single mutation in MCCC1 or MCCC2 as a potential cause of positive
RT screening for 3-methylcrotonyl-CoA carboxylase deficiency.";
RL Mol. Genet. Metab. 105:602-606(2012).
RN [20]
RP VARIANTS MCC1D GLU-46; LYS-56; LEU-65; HIS-123; MET-125; LYS-134; ARG-160;
RP VAL-180; PRO-187; TRP-232; ASP-268; GLN-281; GLY-288; VAL-289; VAL-291;
RP ARG-325; PRO-372; ASP-379; SER-379; PRO-380; SER-385; MET-434; MET-439;
RP MET-460; HIS-532; PHE-535 AND 566-VAL-THR-567 DEL, AND CHARACTERIZATION OF
RP VARIANTS MCC1D GLY-288; ASP-379 AND MET-434.
RX PubMed=22642865; DOI=10.1186/1750-1172-7-31;
RA Gruenert S.C., Stucki M., Morscher R.J., Suormala T., Buerer C., Burda P.,
RA Christensen E., Ficicioglu C., Herwig J., Koelker S., Moeslinger D.,
RA Pasquini E., Santer R., Schwab K.O., Wilcken B., Fowler B., Yue W.W.,
RA Baumgartner M.R.;
RT "3-methylcrotonyl-CoA carboxylase deficiency: clinical, biochemical,
RT enzymatic and molecular studies in 88 individuals.";
RL Orphanet J. Rare Dis. 7:31-54(2012).
RN [21]
RP VARIANTS MCC1D CYS-79; VAL-209; GLY-288; LYS-366 AND HIS-444.
RX PubMed=25382614; DOI=10.1111/cge.12535;
RA Yang L., Yang J., Zhang T., Weng C., Hong F., Tong F., Yang R., Yin X.,
RA Yu P., Huang X., Qi M.;
RT "Identification of eight novel mutations and transcript analysis of two
RT splicing mutations in Chinese newborns with MCC deficiency.";
RL Clin. Genet. 88:484-488(2015).
RN [22]
RP VARIANTS MCC1D PHE-120; SER-130; LYS-383 AND SER-385.
RX PubMed=27601257; DOI=10.1016/j.gene.2016.09.003;
RA Fonseca H., Azevedo L., Serrano C., Sousa C., Marcao A., Vilarinho L.;
RT "3-Methylcrotonyl-CoA carboxylase deficiency: Mutational spectrum derived
RT from comprehensive newborn screening.";
RL Gene 594:203-210(2016).
RN [23]
RP VARIANT SER-632.
RX PubMed=28887846; DOI=10.1002/humu.23335;
RA Zhou X.L., He L.X., Yu L.J., Wang Y., Wang X.J., Wang E.D., Yang T.;
RT "Mutations in KARS cause early-onset hearing loss and leukoencephalopathy:
RT Potential pathogenic mechanism.";
RL Hum. Mutat. 38:1740-1750(2017).
CC -!- FUNCTION: Biotin-attachment subunit of the 3-methylcrotonyl-CoA
CC carboxylase, an enzyme that catalyzes the conversion of 3-
CC methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for
CC leucine and isovaleric acid catabolism. {ECO:0000269|PubMed:17360195}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-methyl-(2E)-butenoyl-CoA + ATP + hydrogencarbonate = 3-
CC methyl-(2E)-glutaconyl-CoA + ADP + H(+) + phosphate;
CC Xref=Rhea:RHEA:13589, ChEBI:CHEBI:15378, ChEBI:CHEBI:17544,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:57344,
CC ChEBI:CHEBI:57346, ChEBI:CHEBI:456216; EC=6.4.1.4;
CC Evidence={ECO:0000269|PubMed:17360195};
CC -!- COFACTOR:
CC Name=biotin; Xref=ChEBI:CHEBI:57586;
CC -!- PATHWAY: Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-
CC 3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.
CC -!- SUBUNIT: Probably a dodecamer composed of six biotin-containing alpha
CC subunits (MCCC1) and six beta (MCCC2) subunits (PubMed:17360195).
CC Interacts (via the biotin carboxylation domain) with SIRT4
CC (PubMed:23438705). {ECO:0000269|PubMed:17360195,
CC ECO:0000269|PubMed:23438705}.
CC -!- INTERACTION:
CC Q96RQ3; Q9HCC0: MCCC2; NbExp=5; IntAct=EBI-2211703, EBI-2211296;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:16023992}.
CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:Q99MR8}.
CC -!- DISEASE: 3-methylcrotonoyl-CoA carboxylase 1 deficiency (MCC1D)
CC [MIM:210200]: An autosomal recessive disorder of leucine catabolism.
CC The phenotype is variable, ranging from neonatal onset with severe
CC neurological involvement to asymptomatic adults. There is a
CC characteristic organic aciduria with massive excretion of 3-
CC hydroxyisovaleric acid and 3-methylcrotonylglycine, usually in
CC combination with a severe secondary carnitine deficiency.
CC {ECO:0000269|PubMed:11170888, ECO:0000269|PubMed:11181649,
CC ECO:0000269|PubMed:11406611, ECO:0000269|PubMed:16010683,
CC ECO:0000269|PubMed:17968484, ECO:0000269|PubMed:21071250,
CC ECO:0000269|PubMed:22150417, ECO:0000269|PubMed:22264772,
CC ECO:0000269|PubMed:22642865, ECO:0000269|PubMed:25382614,
CC ECO:0000269|PubMed:27601257, ECO:0000269|Ref.6}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD92974.1; Type=Erroneous initiation; Note=Extended N-terminus.; 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; AF310972; AAG53095.1; -; mRNA.
DR EMBL; AB029826; BAA99407.1; -; mRNA.
DR EMBL; AF297332; AAK67986.1; -; mRNA.
DR EMBL; AF310339; AAG50245.1; -; mRNA.
DR EMBL; AK023051; BAB14377.1; -; mRNA.
DR EMBL; AB209737; BAD92974.1; ALT_INIT; mRNA.
DR EMBL; BC004214; AAH04214.1; -; mRNA.
DR EMBL; BC004187; AAH04187.1; -; mRNA.
DR CCDS; CCDS3241.1; -.
DR RefSeq; NP_001280202.1; NM_001293273.1.
DR RefSeq; NP_064551.3; NM_020166.4.
DR PDB; 2EJM; NMR; -; A=640-725.
DR PDBsum; 2EJM; -.
DR AlphaFoldDB; Q96RQ3; -.
DR SMR; Q96RQ3; -.
DR BioGRID; 121249; 185.
DR ComplexPortal; CPX-6236; Mitochondrial methylcrotonyl-CoA carboxylase complex.
DR CORUM; Q96RQ3; -.
DR IntAct; Q96RQ3; 40.
DR MINT; Q96RQ3; -.
DR STRING; 9606.ENSP00000265594; -.
DR DrugBank; DB00121; Biotin.
DR GlyGen; Q96RQ3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q96RQ3; -.
DR PhosphoSitePlus; Q96RQ3; -.
DR SwissPalm; Q96RQ3; -.
DR BioMuta; MCCC1; -.
DR DMDM; 108861983; -.
DR EPD; Q96RQ3; -.
DR jPOST; Q96RQ3; -.
DR MassIVE; Q96RQ3; -.
DR MaxQB; Q96RQ3; -.
DR PaxDb; Q96RQ3; -.
DR PeptideAtlas; Q96RQ3; -.
DR PRIDE; Q96RQ3; -.
DR ProteomicsDB; 78003; -.
DR Antibodypedia; 1557; 176 antibodies from 23 providers.
DR DNASU; 56922; -.
DR Ensembl; ENST00000265594.9; ENSP00000265594.4; ENSG00000078070.14.
DR GeneID; 56922; -.
DR KEGG; hsa:56922; -.
DR MANE-Select; ENST00000265594.9; ENSP00000265594.4; NM_020166.5; NP_064551.3.
DR UCSC; uc003fle.4; human.
DR CTD; 56922; -.
DR DisGeNET; 56922; -.
DR GeneCards; MCCC1; -.
DR HGNC; HGNC:6936; MCCC1.
DR HPA; ENSG00000078070; Low tissue specificity.
DR MalaCards; MCCC1; -.
DR MIM; 210200; phenotype.
DR MIM; 609010; gene.
DR neXtProt; NX_Q96RQ3; -.
DR OpenTargets; ENSG00000078070; -.
DR Orphanet; 6; 3-methylcrotonyl-CoA carboxylase deficiency.
DR PharmGKB; PA30680; -.
DR VEuPathDB; HostDB:ENSG00000078070; -.
DR eggNOG; KOG0238; Eukaryota.
DR GeneTree; ENSGT00940000156941; -.
DR HOGENOM; CLU_000395_3_1_1; -.
DR InParanoid; Q96RQ3; -.
DR OMA; FVEICSH; -.
DR OrthoDB; 254436at2759; -.
DR PhylomeDB; Q96RQ3; -.
DR TreeFam; TF105650; -.
DR BioCyc; MetaCyc:ENSG00000078070-MON; -.
DR PathwayCommons; Q96RQ3; -.
DR Reactome; R-HSA-196780; Biotin transport and metabolism.
DR Reactome; R-HSA-3371599; Defective HLCS causes multiple carboxylase deficiency.
DR Reactome; R-HSA-70895; Branched-chain amino acid catabolism.
DR SignaLink; Q96RQ3; -.
DR UniPathway; UPA00363; UER00861.
DR BioGRID-ORCS; 56922; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; MCCC1; human.
DR EvolutionaryTrace; Q96RQ3; -.
DR GenomeRNAi; 56922; -.
DR Pharos; Q96RQ3; Tbio.
DR PRO; PR:Q96RQ3; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q96RQ3; protein.
DR Bgee; ENSG00000078070; Expressed in body of pancreas and 195 other tissues.
DR ExpressionAtlas; Q96RQ3; baseline and differential.
DR Genevisible; Q96RQ3; HS.
DR GO; GO:0002169; C:3-methylcrotonyl-CoA carboxylase complex, mitochondrial; IPI:ComplexPortal.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:1905202; C:methylcrotonoyl-CoA carboxylase complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:ParkinsonsUK-UCL.
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; NAS:UniProtKB.
DR GO; GO:0004075; F:biotin carboxylase activity; NAS:ParkinsonsUK-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0004485; F:methylcrotonoyl-CoA carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006768; P:biotin metabolic process; NAS:UniProtKB.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IC:ComplexPortal.
DR GO; GO:0006552; P:leucine catabolic process; ISS:ParkinsonsUK-UCL.
DR InterPro; IPR011761; ATP-grasp.
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; 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 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; PS00867; CPSASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Biotin; Direct protein sequencing;
KW Disease variant; Ligase; Mitochondrion; Nucleotide-binding;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..41
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:16023992"
FT CHAIN 42..725
FT /note="Methylcrotonoyl-CoA carboxylase subunit alpha,
FT mitochondrial"
FT /id="PRO_0000002833"
FT DOMAIN 48..494
FT /note="Biotin carboxylation"
FT DOMAIN 167..364
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 643..715
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT ACT_SITE 339
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 247
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 282
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 237
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MR8"
FT MOD_RES 494
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99MR8"
FT MOD_RES 581
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MR8"
FT MOD_RES 581
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99MR8"
FT MOD_RES 681
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000250, ECO:0000255|PROSITE-
FT ProRule:PRU01066"
FT VARIANT 46
FT /note="G -> E (in MCC1D; dbSNP:rs199517715)"
FT /evidence="ECO:0000269|PubMed:21071250,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072486"
FT VARIANT 56
FT /note="N -> K (in MCC1D; dbSNP:rs1057520695)"
FT /evidence="ECO:0000269|PubMed:22264772,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072487"
FT VARIANT 65
FT /note="M -> L (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072488"
FT VARIANT 79
FT /note="Y -> C (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077284"
FT VARIANT 120
FT /note="S -> F (in MCC1D; dbSNP:rs1307589698)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077285"
FT VARIANT 123
FT /note="Q -> H (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072489"
FT VARIANT 125
FT /note="I -> M (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072490"
FT VARIANT 130
FT /note="G -> S (in MCC1D; clinically asymptomatic form;
FT dbSNP:rs202197951)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077286"
FT VARIANT 134
FT /note="E -> K (in MCC1D; dbSNP:rs1229069160)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072491"
FT VARIANT 160
FT /note="M -> R (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072492"
FT VARIANT 180
FT /note="G -> V (in MCC1D; dbSNP:rs748201122)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072493"
FT VARIANT 187
FT /note="S -> P (in MCC1D; dbSNP:rs757362635)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072494"
FT VARIANT 209
FT /note="G -> V (in MCC1D; dbSNP:rs186209189)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077287"
FT VARIANT 232
FT /note="R -> W (in MCC1D; dbSNP:rs727504004)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072495"
FT VARIANT 268
FT /note="A -> D (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072496"
FT VARIANT 276
FT /note="C -> R (in MCC1D; dbSNP:rs773433541)"
FT /evidence="ECO:0000269|PubMed:22150417"
FT /id="VAR_067197"
FT VARIANT 281
FT /note="R -> Q (in MCC1D; dbSNP:rs754437245)"
FT /evidence="ECO:0000269|PubMed:22150417,
FT ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865"
FT /id="VAR_067198"
FT VARIANT 288
FT /note="E -> G (in MCC1D; shows no residual activity;
FT dbSNP:rs746500530)"
FT /evidence="ECO:0000269|PubMed:22642865,
FT ECO:0000269|PubMed:25382614"
FT /id="VAR_072497"
FT VARIANT 289
FT /note="A -> V (in MCC1D; mild form; dbSNP:rs1326114075)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012785"
FT VARIANT 291
FT /note="A -> V (in MCC1D; associated with a reduction of
FT wild-type residual activity; dbSNP:rs201041864)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072498"
FT VARIANT 325
FT /note="M -> R (in MCC1D; dbSNP:rs119103212)"
FT /evidence="ECO:0000269|PubMed:11170888,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012786"
FT VARIANT 366
FT /note="E -> K (in MCC1D; unknown pathological significance;
FT dbSNP:rs201386261)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077288"
FT VARIANT 372
FT /note="Q -> P (in MCC1D; dbSNP:rs755328329)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072499"
FT VARIANT 379
FT /note="G -> D (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072500"
FT VARIANT 379
FT /note="G -> S (in MCC1D; dbSNP:rs887877405)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072501"
FT VARIANT 380
FT /note="H -> P (in MCC1D; dbSNP:rs794727036)"
FT /evidence="ECO:0000269|PubMed:22264772,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072502"
FT VARIANT 383
FT /note="E -> K (in MCC1D; unknown pathological significance;
FT dbSNP:rs1333357031)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077289"
FT VARIANT 385
FT /note="R -> S (in MCC1D; severe form; dbSNP:rs119103213)"
FT /evidence="ECO:0000269|PubMed:11170888,
FT ECO:0000269|PubMed:11181649, ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865,
FT ECO:0000269|PubMed:27601257"
FT /id="VAR_012787"
FT VARIANT 434
FT /note="I -> M (in MCC1D; shows some wild-type residual
FT activity; dbSNP:rs376289130)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072503"
FT VARIANT 437
FT /note="L -> P (in MCC1D; severe form; dbSNP:rs119103215)"
FT /evidence="ECO:0000269|PubMed:11181649"
FT /id="VAR_012788"
FT VARIANT 439
FT /note="V -> M (in MCC1D; dbSNP:rs398124352)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072504"
FT VARIANT 444
FT /note="R -> H (in MCC1D; dbSNP:rs768785753)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077290"
FT VARIANT 460
FT /note="I -> M (in MCC1D; dbSNP:rs119103218)"
FT /evidence="ECO:0000269|PubMed:17968484,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072505"
FT VARIANT 464
FT /note="H -> P (in dbSNP:rs2270968)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:11406611, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.6"
FT /id="VAR_012789"
FT VARIANT 532
FT /note="D -> H (in MCC1D; severe form; dbSNP:rs119103214)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012790"
FT VARIANT 535
FT /note="S -> F (in MCC1D; asymptomatic form;
FT dbSNP:rs119103216)"
FT /evidence="ECO:0000269|PubMed:11406611,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012791"
FT VARIANT 560
FT /note="N -> T (in dbSNP:rs35219417)"
FT /id="VAR_038631"
FT VARIANT 566..567
FT /note="Missing (in MCC1D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072506"
FT VARIANT 632
FT /note="P -> S (in dbSNP:rs142867987)"
FT /evidence="ECO:0000269|PubMed:28887846"
FT /id="VAR_079752"
FT CONFLICT 469
FT /note="F -> L (in Ref. 3; AAK67986)"
FT /evidence="ECO:0000305"
FT STRAND 652..660
FT /evidence="ECO:0007829|PDB:2EJM"
FT STRAND 666..668
FT /evidence="ECO:0007829|PDB:2EJM"
FT STRAND 673..687
FT /evidence="ECO:0007829|PDB:2EJM"
FT STRAND 692..698
FT /evidence="ECO:0007829|PDB:2EJM"
FT STRAND 703..705
FT /evidence="ECO:0007829|PDB:2EJM"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:2EJM"
SQ SEQUENCE 725 AA; 80473 MW; B84AD23806035A40 CRC64;
MAAASAVSVL LVAAERNRWH RLPSLLLPPR TWVWRQRTMK YTTATGRNIT KVLIANRGEI
ACRVMRTAKK LGVQTVAVYS EADRNSMHVD MADEAYSIGP APSQQSYLSM EKIIQVAKTS
AAQAIHPGCG FLSENMEFAE LCKQEGIIFI GPPPSAIRDM GIKSTSKSIM AAAGVPVVEG
YHGEDQSDQC LKEHARRIGY PVMIKAVRGG GGKGMRIVRS EQEFQEQLES ARREAKKSFN
DDAMLIEKFV DTPRHVEVQV FGDHHGNAVY LFERDCSVQR RHQKIIEEAP APGIKSEVRK
KLGEAAVRAA KAVNYVGAGT VEFIMDSKHN FCFMEMNTRL QVEHPVTEMI TGTDLVEWQL
RIAAGEKIPL SQEEITLQGH AFEARIYAED PSNNFMPVAG PLVHLSTPRA DPSTRIETGV
RQGDEVSVHY DPMIAKLVVW AADRQAALTK LRYSLRQYNI VGLHTNIDFL LNLSGHPEFE
AGNVHTDFIP QHHKQLLLSR KAAAKESLCQ AALGLILKEK AMTDTFTLQA HDQFSPFSSS
SGRRLNISYT RNMTLKDGKN NVAIAVTYNH DGSYSMQIED KTFQVLGNLY SEGDCTYLKC
SVNGVASKAK LIILENTIYL FSKEGSIEID IPVPKYLSSV SSQETQGGPL APMTGTIEKV
FVKAGDKVKA GDSLMVMIAM KMEHTIKSPK DGTVKKVFYR EGAQANRHTP LVEFEEEESD
KRESE
