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 27-MAR-2024, entry version 205. 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 VARIANT MCC2D VAL-437. RX PubMed=14680978; DOI=10.1016/s1096-7192(03)00130-6; RA Desviat L.R., Perez-Cerda C., Perez B., Esparza-Gordillo J., RA Rodriguez-Pombo P., Penalva M.A., Rodriguez De Cordoba S., Ugarte M.; RT "Functional analysis of MCCA and MCCB mutations causing RT methylcrotonylglycinuria."; RL Mol. Genet. Metab. 80:315-320(2003). RN [15] 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 [16] 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 [17] 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 [18] 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 [19] 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 [20] 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 [21] 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 [22] 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; P13569: CFTR; NbExp=5; IntAct=EBI-2211296, EBI-349854; 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:14680978, CC ECO:0000269|PubMed:16010683, ECO:0000269|PubMed:17968484, CC ECO:0000269|PubMed:21071250, ECO:0000269|PubMed:22150417, CC ECO:0000269|PubMed:22264772, ECO:0000269|PubMed:22642865, CC ECO:0000269|PubMed:25382614, ECO:0000269|PubMed:27601257}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the AccD/PCCB family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH14897.1; 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; 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 CCDS; CCDS93731.1; -. [Q9HCC0-2] 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; 162. DR ComplexPortal; CPX-6236; Mitochondrial methylcrotonyl-CoA carboxylase complex. DR CORUM; Q9HCC0; -. DR IntAct; Q9HCC0; 45. 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 SwissPalm; 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; 9606-ENSP00000343657; -. DR PeptideAtlas; Q9HCC0; -. DR ProteomicsDB; 81665; -. [Q9HCC0-1] DR ProteomicsDB; 81666; -. [Q9HCC0-2] DR Pumba; Q9HCC0; -. DR Antibodypedia; 24162; 310 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 AGR; HGNC:6937; -. 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 OrthoDB; 5474505at2759; -. DR PhylomeDB; Q9HCC0; -. DR TreeFam; TF300446; -. DR BioCyc; MetaCyc:ENSG00000131844-MONOMER; -. 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; 13 hits in 1170 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 181 other cell types or tissues. DR ExpressionAtlas; Q9HCC0; baseline and differential. 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; NAS: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_beta. 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; ACETYL, PROPIONYL, PYRUVATE, AND GLUTACONYL CARBOXYLASE-RELATED; 1. DR PANTHER; PTHR22855:SF13; METHYLCROTONOYL-COA CARBOXYLASE BETA CHAIN, MITOCHONDRIAL; 1. DR Pfam; PF01039; Carboxyl_trans; 1. DR SUPFAM; SSF52096; ClpP/crotonase; 2. DR PROSITE; PS50989; COA_CT_CTER; 1. DR PROSITE; PS50980; COA_CT_NTER; 1. DR Genevisible; Q9HCC0; HS. 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; uncertain 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; uncertain 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; uncertain 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 FT wild-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; uncertain 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 FT wild-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; uncertain 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 /evidence="ECO:0000269|PubMed:14680978" FT /id="VAR_012801" FT VARIANT 441 FT /note="I -> T (in MCC2D; uncertain 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 //