MCCB_HUMAN
ID MCCB_HUMAN Reviewed; 563 AA.
AC Q9HCC0; A6NIY9; Q96C27; Q9Y4L7;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Methylcrotonoyl-CoA carboxylase beta chain, mitochondrial;
DE Short=MCCase subunit beta;
DE EC=6.4.1.4 {ECO:0000269|PubMed:17360195};
DE AltName: Full=3-methylcrotonyl-CoA carboxylase 2;
DE AltName: Full=3-methylcrotonyl-CoA carboxylase non-biotin-containing subunit;
DE AltName: Full=3-methylcrotonyl-CoA:carbon dioxide ligase subunit beta;
DE Flags: Precursor;
GN Name=MCCC2; Synonyms=MCCB;
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).
RA Fukuda T., Otsuka H., Morishita R., Takemoto Y., Sone M., Nakao M., Abe S.,
RA Kondo I.;
RT "Human non-biotin containing subunit gene of 3-methylcrotonyl-CoA
RT carboxylase (MCCB).";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND VARIANTS
RP MCC2D ARG-167 AND THR-218.
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS MCC2D GLN-99; GLN-155;
RP LEU-173; CYS-193; ARG-310 AND MET-339.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MCC2D THR-268.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Testis, and Uterus;
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 23-28, 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, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 469-563.
RG The European IMAGE consortium;
RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
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 [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 VARIANTS MCC2D ARG-190; VAL-218 AND TYR-280.
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 [15]
RP VARIANTS MCC2D GLN-99; TRP-155; GLN-155; TYR-190; THR-268; ARG-282;
RP ARG-310; PHE-375 AND VAL-456, AND CHARACTERIZATION OF VARIANTS TYR-190 AND
RP ARG-352.
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 VARIANTS MCC2D PHE-355; ARG-477; ARG-517 AND SER-520.
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 [17]
RP VARIANTS MCC2D TYR-280 AND SER-459.
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 [18]
RP VARIANTS MCC2D VAL-218; MET-339 AND GLY-523.
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 [19]
RP VARIANTS MCC2D PHE-39; GLN-99; PHE-101; GLY-118 DEL; PHE-131; ASN-146;
RP THR-152; TRP-155; ARG-167; ASP-169; LEU-173; ARG-190; TYR-190; CYS-193;
RP HIS-193; ASN-200; THR-218; VAL-218; GLU-220; LEU-224; ASP-237; LEU-266;
RP TYR-280; ARG-282; ARG-310; MET-339; VAL-340 ARG-352; PHE-355; PHE-375;
RP THR-403; LEU-434; VAL-456; ARG-475; ARG-477; ARG-517; SER-520; GLY-523 AND
RP GLU-555, AND CHARACTERIZATION OF VARIANTS MCC2D PHE-39; GLY-118 DEL;
RP ASN-146; ARG-282; LEU-434; VAL-456; ARG-475 AND GLY-523.
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 [20]
RP VARIANTS MCC2D ILE-139 AND ARG-319.
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 [21]
RP VARIANTS MCC2D VAL-68; ARG-105; TRP-155; ASP-163; ASN-200; ALA-214;
RP TRP-216; THR-218; ASP-230; CYS-318; MET-339; VAL-387; PRO-393; ARG-410;
RP ASP-410; THR-441; VAL-461; ARG-475 AND THR-524.
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).
CC -!- FUNCTION: Carboxyltransferase 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=45 uM for ATP {ECO:0000269|PubMed:17360195};
CC KM=74 uM for 3-methylcrotonyl-CoA {ECO:0000269|PubMed:17360195};
CC Note=kcat is 4.0 sec(-1).;
CC -!- PATHWAY: Amino-acid degradation; L-leucine degradation; (S)-3-hydroxy-
CC 3-methylglutaryl-CoA from 3-isovaleryl-CoA: step 2/3.
CC {ECO:0000269|PubMed:17360195}.
CC -!- SUBUNIT: Probably a dodecamer composed of six biotin-containing alpha
CC subunits (MCCC1) and six beta (MCCC2) subunits.
CC -!- INTERACTION:
CC Q9HCC0; Q96RQ3: MCCC1; NbExp=5; IntAct=EBI-2211296, EBI-2211703;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:11170888, ECO:0000269|PubMed:16023992}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HCC0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9HCC0-2; Sequence=VSP_000069;
CC -!- DISEASE: 3-methylcrotonoyl-CoA carboxylase 2 deficiency (MCC2D)
CC [MIM:210210]: 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}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the AccD/PCCB family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH14897.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AB050049; BAB16880.1; -; mRNA.
DR EMBL; AB050050; BAB41121.1; -; Genomic_DNA.
DR EMBL; AF310971; AAG53094.1; -; mRNA.
DR EMBL; AF301000; AAK16404.1; -; mRNA.
DR EMBL; AF261884; AAK49409.1; -; mRNA.
DR EMBL; AC138832; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471084; EAW95693.1; -; Genomic_DNA.
DR EMBL; BC014897; AAH14897.1; ALT_FRAME; mRNA.
DR EMBL; BC065027; AAH65027.1; -; mRNA.
DR EMBL; AL079298; CAB45194.1; -; mRNA.
DR CCDS; CCDS34184.1; -. [Q9HCC0-1]
DR RefSeq; NP_071415.1; NM_022132.4. [Q9HCC0-1]
DR RefSeq; XP_005248624.1; XM_005248567.1.
DR AlphaFoldDB; Q9HCC0; -.
DR SMR; Q9HCC0; -.
DR BioGRID; 122050; 112.
DR ComplexPortal; CPX-6236; Mitochondrial methylcrotonyl-CoA carboxylase complex.
DR CORUM; Q9HCC0; -.
DR IntAct; Q9HCC0; 42.
DR MINT; Q9HCC0; -.
DR STRING; 9606.ENSP00000343657; -.
DR DrugBank; DB00121; Biotin.
DR GlyGen; Q9HCC0; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HCC0; -.
DR PhosphoSitePlus; Q9HCC0; -.
DR BioMuta; MCCC2; -.
DR DMDM; 20138731; -.
DR REPRODUCTION-2DPAGE; IPI00784044; -.
DR CPTAC; CPTAC-405; -.
DR CPTAC; CPTAC-406; -.
DR EPD; Q9HCC0; -.
DR jPOST; Q9HCC0; -.
DR MassIVE; Q9HCC0; -.
DR MaxQB; Q9HCC0; -.
DR PaxDb; Q9HCC0; -.
DR PeptideAtlas; Q9HCC0; -.
DR PRIDE; Q9HCC0; -.
DR ProteomicsDB; 81665; -. [Q9HCC0-1]
DR ProteomicsDB; 81666; -. [Q9HCC0-2]
DR Antibodypedia; 24162; 281 antibodies from 29 providers.
DR DNASU; 64087; -.
DR Ensembl; ENST00000340941.11; ENSP00000343657.6; ENSG00000131844.17. [Q9HCC0-1]
DR Ensembl; ENST00000683789.1; ENSP00000507012.1; ENSG00000131844.17. [Q9HCC0-2]
DR GeneID; 64087; -.
DR KEGG; hsa:64087; -.
DR MANE-Select; ENST00000340941.11; ENSP00000343657.6; NM_022132.5; NP_071415.1.
DR UCSC; uc003kbs.5; human. [Q9HCC0-1]
DR CTD; 64087; -.
DR DisGeNET; 64087; -.
DR GeneCards; MCCC2; -.
DR HGNC; HGNC:6937; MCCC2.
DR HPA; ENSG00000131844; Tissue enhanced (liver).
DR MalaCards; MCCC2; -.
DR MIM; 210210; phenotype.
DR MIM; 609014; gene.
DR neXtProt; NX_Q9HCC0; -.
DR OpenTargets; ENSG00000131844; -.
DR Orphanet; 6; 3-methylcrotonyl-CoA carboxylase deficiency.
DR PharmGKB; PA30681; -.
DR VEuPathDB; HostDB:ENSG00000131844; -.
DR eggNOG; KOG0540; Eukaryota.
DR GeneTree; ENSGT00940000155949; -.
DR HOGENOM; CLU_018822_0_1_1; -.
DR InParanoid; Q9HCC0; -.
DR OMA; AYLPIMS; -.
DR PhylomeDB; Q9HCC0; -.
DR TreeFam; TF300446; -.
DR BioCyc; MetaCyc:ENSG00000131844-MON; -.
DR PathwayCommons; Q9HCC0; -.
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; Q9HCC0; -.
DR UniPathway; UPA00363; UER00861.
DR BioGRID-ORCS; 64087; 12 hits in 1079 CRISPR screens.
DR ChiTaRS; MCCC2; human.
DR GenomeRNAi; 64087; -.
DR Pharos; Q9HCC0; Tbio.
DR PRO; PR:Q9HCC0; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9HCC0; protein.
DR Bgee; ENSG00000131844; Expressed in left ventricle myocardium and 179 other tissues.
DR ExpressionAtlas; Q9HCC0; baseline and differential.
DR Genevisible; Q9HCC0; 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:ParkinsonsUK-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004485; F:methylcrotonoyl-CoA carboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0009083; P:branched-chain amino acid catabolic process; IC:ComplexPortal.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:Ensembl.
DR GO; GO:0006552; P:leucine catabolic process; IBA:GO_Central.
DR InterPro; IPR034733; AcCoA_carboxyl.
DR InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR InterPro; IPR011763; COA_CT_C.
DR InterPro; IPR011762; COA_CT_N.
DR InterPro; IPR045190; MCCB/AccD1-like.
DR PANTHER; PTHR22855; PTHR22855; 1.
DR Pfam; PF01039; Carboxyl_trans; 1.
DR SUPFAM; SSF52096; SSF52096; 2.
DR PROSITE; PS50989; COA_CT_CTER; 1.
DR PROSITE; PS50980; COA_CT_NTER; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; ATP-binding; Direct protein sequencing;
KW Disease variant; Ligase; Mitochondrion; Nucleotide-binding;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..22
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:16023992"
FT CHAIN 23..563
FT /note="Methylcrotonoyl-CoA carboxylase beta chain,
FT mitochondrial"
FT /id="PRO_0000000291"
FT DOMAIN 49..306
FT /note="CoA carboxyltransferase N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01136"
FT DOMAIN 309..555
FT /note="CoA carboxyltransferase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01137"
FT REGION 49..555
FT /note="Carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01138"
FT REGION 343..372
FT /note="Acyl-CoA binding"
FT /evidence="ECO:0000255"
FT MOD_RES 70
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT MOD_RES 70
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT MOD_RES 141
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT MOD_RES 495
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT MOD_RES 495
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT MOD_RES 511
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q3ULD5"
FT VAR_SEQ 209..246
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_000069"
FT VARIANT 39
FT /note="S -> F (in MCC2D; has some wild-type residual
FT activity; dbSNP:rs398124371)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072507"
FT VARIANT 68
FT /note="G -> V (in MCC2D; unknown pathological significance;
FT dbSNP:rs1187203558)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077291"
FT VARIANT 99
FT /note="E -> Q (in MCC2D; severe and mild form;
FT dbSNP:rs119103219)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:16010683, ECO:0000269|PubMed:22642865"
FT /id="VAR_012792"
FT VARIANT 101
FT /note="S -> F (in MCC2D; dbSNP:rs748028684)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072508"
FT VARIANT 105
FT /note="G -> R (in MCC2D; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077292"
FT VARIANT 118
FT /note="Missing (in MCC2D; has some wild-type residual
FT activity)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072509"
FT VARIANT 131
FT /note="C -> F (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072510"
FT VARIANT 139
FT /note="T -> I (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077293"
FT VARIANT 146
FT /note="Y -> N (in MCC2D; has some wild-type residual
FT activity)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072511"
FT VARIANT 152
FT /note="K -> T (in MCC2D; dbSNP:rs1554134065)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072512"
FT VARIANT 155
FT /note="R -> Q (in MCC2D; mild form; dbSNP:rs119103220)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:16010683"
FT /id="VAR_012793"
FT VARIANT 155
FT /note="R -> W (in MCC2D; dbSNP:rs141030969)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865, ECO:0000269|PubMed:27601257"
FT /id="VAR_072513"
FT VARIANT 163
FT /note="N -> D (in MCC2D; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077294"
FT VARIANT 167
FT /note="C -> R (in MCC2D; dbSNP:rs119103222)"
FT /evidence="ECO:0000269|PubMed:11170888,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012794"
FT VARIANT 169
FT /note="Y -> D (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072514"
FT VARIANT 173
FT /note="S -> L (in MCC2D; severe form; dbSNP:rs752866557)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012795"
FT VARIANT 190
FT /note="H -> R (in MCC2D; dbSNP:rs119103225)"
FT /evidence="ECO:0000269|PubMed:17968484,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072515"
FT VARIANT 190
FT /note="H -> Y (in MCC2D; produces severely decreased wild-
FT type residual activity; dbSNP:rs773774134)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072516"
FT VARIANT 193
FT /note="R -> C (in MCC2D; mild form; dbSNP:rs547662164)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_012796"
FT VARIANT 193
FT /note="R -> H (in MCC2D; dbSNP:rs535519604)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072517"
FT VARIANT 200
FT /note="I -> N (in MCC2D; unknown pathological significance;
FT dbSNP:rs140806722)"
FT /evidence="ECO:0000269|PubMed:22642865,
FT ECO:0000269|PubMed:27601257"
FT /id="VAR_072518"
FT VARIANT 214
FT /note="G -> A (in MCC2D; dbSNP:rs277995)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077295"
FT VARIANT 216
FT /note="C -> W (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077296"
FT VARIANT 218
FT /note="A -> T (in MCC2D; dbSNP:rs886043524)"
FT /evidence="ECO:0000269|PubMed:11170888,
FT ECO:0000269|PubMed:22642865, ECO:0000269|PubMed:27601257"
FT /id="VAR_012797"
FT VARIANT 218
FT /note="A -> V (in MCC2D; dbSNP:rs760420191)"
FT /evidence="ECO:0000269|PubMed:17968484,
FT ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865"
FT /id="VAR_072519"
FT VARIANT 220
FT /note="G -> E (in MCC2D; dbSNP:rs1254750166)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072520"
FT VARIANT 224
FT /note="P -> L (in MCC2D; dbSNP:rs1195601465)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072521"
FT VARIANT 230
FT /note="N -> D (in MCC2D; dbSNP:rs766753795)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077297"
FT VARIANT 237
FT /note="G -> D (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072522"
FT VARIANT 266
FT /note="H -> L (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072523"
FT VARIANT 268
FT /note="R -> T (in MCC2D; asymptomatic form;
FT dbSNP:rs119103223)"
FT /evidence="ECO:0000269|PubMed:11406611,
FT ECO:0000269|PubMed:16010683"
FT /id="VAR_012798"
FT VARIANT 268
FT /note="Missing (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:16010683"
FT /id="VAR_072524"
FT VARIANT 280
FT /note="D -> Y (in MCC2D; dbSNP:rs119103226)"
FT /evidence="ECO:0000269|PubMed:17968484,
FT ECO:0000269|PubMed:22150417, ECO:0000269|PubMed:22642865"
FT /id="VAR_067199"
FT VARIANT 282
FT /note="H -> R (in MCC2D; has some wild-type residual
FT activity)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072525"
FT VARIANT 310
FT /note="P -> R (in MCC2D; mild form; dbSNP:rs119103221)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:16010683, ECO:0000269|PubMed:22642865"
FT /id="VAR_012799"
FT VARIANT 318
FT /note="Y -> C (in MCC2D; dbSNP:rs773115035)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077298"
FT VARIANT 319
FT /note="G -> R (in MCC2D; dbSNP:rs1443551700)"
FT /evidence="ECO:0000269|PubMed:25382614"
FT /id="VAR_077299"
FT VARIANT 339
FT /note="V -> M (in MCC2D; severe form; dbSNP:rs150591260)"
FT /evidence="ECO:0000269|PubMed:11181649,
FT ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865,
FT ECO:0000269|PubMed:27601257"
FT /id="VAR_012800"
FT VARIANT 340
FT /note="D -> V (in MCC2D; dbSNP:rs398124370)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072526"
FT VARIANT 352
FT /note="G -> R (in MCC2D; produces severely decreased wild-
FT type residual activity; dbSNP:rs765438239)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072527"
FT VARIANT 355
FT /note="L -> F (in MCC2D; dbSNP:rs757052602)"
FT /evidence="ECO:0000269|PubMed:21071250,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072528"
FT VARIANT 375
FT /note="V -> F (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072529"
FT VARIANT 387
FT /note="F -> V (in MCC2D; unknown pathological significance;
FT dbSNP:rs1450515408)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077300"
FT VARIANT 393
FT /note="Q -> P (in MCC2D; dbSNP:rs750782118)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077301"
FT VARIANT 403
FT /note="N -> T (in MCC2D; dbSNP:rs142887940)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072530"
FT VARIANT 410
FT /note="G -> D (in MCC2D; dbSNP:rs771440617)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077302"
FT VARIANT 410
FT /note="G -> R (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077303"
FT VARIANT 434
FT /note="V -> L (in MCC2D; has some wild-type residual
FT activity; dbSNP:rs758506791)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072531"
FT VARIANT 437
FT /note="I -> V (in MCC2D; mild form; dbSNP:rs119103224)"
FT /id="VAR_012801"
FT VARIANT 441
FT /note="I -> T (in MCC2D; unknown pathological significance;
FT dbSNP:rs139852818)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077304"
FT VARIANT 456
FT /note="A -> V (in MCC2D; shows virtually no enzyme
FT activity; dbSNP:rs727504011)"
FT /evidence="ECO:0000269|PubMed:16010683,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072532"
FT VARIANT 459
FT /note="P -> S (in MCC2D; dbSNP:rs754741111)"
FT /evidence="ECO:0000269|PubMed:22150417"
FT /id="VAR_067200"
FT VARIANT 461
FT /note="F -> V (in MCC2D)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077305"
FT VARIANT 475
FT /note="G -> R (in MCC2D; has some wild-type residual
FT activity; dbSNP:rs148773718)"
FT /evidence="ECO:0000269|PubMed:22642865,
FT ECO:0000269|PubMed:27601257"
FT /id="VAR_072533"
FT VARIANT 477
FT /note="Q -> R (in MCC2D; dbSNP:rs769558016)"
FT /evidence="ECO:0000269|PubMed:21071250,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072534"
FT VARIANT 478
FT /note="A -> G (in dbSNP:rs35068278)"
FT /id="VAR_038630"
FT VARIANT 517
FT /note="G -> R (in MCC2D; dbSNP:rs979584886)"
FT /evidence="ECO:0000269|PubMed:21071250,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072535"
FT VARIANT 520
FT /note="Y -> S (in MCC2D; dbSNP:rs150327768)"
FT /evidence="ECO:0000269|PubMed:21071250,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072536"
FT VARIANT 523
FT /note="S -> G (in MCC2D; has some wild-type residual
FT activity; dbSNP:rs1459143051)"
FT /evidence="ECO:0000269|PubMed:22264772,
FT ECO:0000269|PubMed:22642865"
FT /id="VAR_072537"
FT VARIANT 524
FT /note="A -> T (in MCC2D; dbSNP:rs774241918)"
FT /evidence="ECO:0000269|PubMed:27601257"
FT /id="VAR_077306"
FT VARIANT 555
FT /note="K -> E (in MCC2D; dbSNP:rs1257849672)"
FT /evidence="ECO:0000269|PubMed:22642865"
FT /id="VAR_072538"
SQ SEQUENCE 563 AA; 61333 MW; 8E3D401AF52DC7D2 CRC64;
MWAVLRLALR PCARASPAGP RAYHGDSVAS LGTQPDLGSA LYQENYKQMK ALVNQLHERV
EHIKLGGGEK ARALHISRGK LLPRERIDNL IDPGSPFLEL SQFAGYQLYD NEEVPGGGII
TGIGRVSGVE CMIIANDATV KGGAYYPVTV KKQLRAQEIA MQNRLPCIYL VDSGGAYLPR
QADVFPDRDH FGRTFYNQAI MSSKNIAQIA VVMGSCTAGG AYVPAMADEN IIVRKQGTIF
LAGPPLVKAA TGEEVSAEDL GGADLHCRKS GVSDHWALDD HHALHLTRKV VRNLNYQKKL
DVTIEPSEEP LFPADELYGI VGANLKRSFD VREVIARIVD GSRFTEFKAF YGDTLVTGFA
RIFGYPVGIV GNNGVLFSES AKKGTHFVQL CCQRNIPLLF LQNITGFMVG REYEAEGIAK
DGAKMVAAVA CAQVPKITLI IGGSYGAGNY GMCGRAYSPR FLYIWPNARI SVMGGEQAAN
VLATITKDQR AREGKQFSSA DEAALKEPII KKFEEEGNPY YSSARVWDDG IIDPADTRLV
LGLSFSAALN APIEKTDFGI FRM
