MCCA_MOUSE
ID MCCA_MOUSE Reviewed; 717 AA.
AC Q99MR8; Q3TGU0; Q9D8R2;
DT 05-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 05-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 183.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic limb, Heart, and Pancreas;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP INTERACTION WITH SIRT4, AND ACETYLATION.
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 [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-577, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-180; LYS-193; LYS-233; LYS-490
RP AND LYS-577, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
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:0000250}.
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 -!- 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 (By similarity).
CC Interacts (via the biotin carboxylation domain) with SIRT4
CC (PubMed:23438705). {ECO:0000250|UniProtKB:Q96RQ3,
CC ECO:0000269|PubMed:23438705}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
CC -!- PTM: Acetylated. {ECO:0000269|PubMed:23438705}.
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DR EMBL; AF310338; AAG50244.1; -; mRNA.
DR EMBL; AK007782; BAB25253.1; -; mRNA.
DR EMBL; AK031072; BAC27239.1; -; mRNA.
DR EMBL; AK168589; BAE40458.1; -; mRNA.
DR EMBL; BC021382; AAH21382.1; -; mRNA.
DR CCDS; CCDS17307.1; -.
DR RefSeq; NP_076133.3; NM_023644.4.
DR AlphaFoldDB; Q99MR8; -.
DR SMR; Q99MR8; -.
DR BioGRID; 215108; 20.
DR IntAct; Q99MR8; 10.
DR MINT; Q99MR8; -.
DR STRING; 10090.ENSMUSP00000029259; -.
DR iPTMnet; Q99MR8; -.
DR PhosphoSitePlus; Q99MR8; -.
DR SwissPalm; Q99MR8; -.
DR EPD; Q99MR8; -.
DR jPOST; Q99MR8; -.
DR MaxQB; Q99MR8; -.
DR PaxDb; Q99MR8; -.
DR PeptideAtlas; Q99MR8; -.
DR PRIDE; Q99MR8; -.
DR ProteomicsDB; 287327; -.
DR Antibodypedia; 1557; 176 antibodies from 23 providers.
DR DNASU; 72039; -.
DR Ensembl; ENSMUST00000029259; ENSMUSP00000029259; ENSMUSG00000027709.
DR GeneID; 72039; -.
DR KEGG; mmu:72039; -.
DR UCSC; uc008oyy.3; mouse.
DR CTD; 56922; -.
DR MGI; MGI:1919289; Mccc1.
DR VEuPathDB; HostDB:ENSMUSG00000027709; -.
DR eggNOG; KOG0238; Eukaryota.
DR GeneTree; ENSGT00940000156941; -.
DR HOGENOM; CLU_000395_3_1_1; -.
DR InParanoid; Q99MR8; -.
DR OMA; FVEICSH; -.
DR OrthoDB; 254436at2759; -.
DR PhylomeDB; Q99MR8; -.
DR TreeFam; TF105650; -.
DR Reactome; R-MMU-196780; Biotin transport and metabolism.
DR Reactome; R-MMU-70895; Branched-chain amino acid catabolism.
DR UniPathway; UPA00363; UER00861.
DR BioGRID-ORCS; 72039; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Mccc1; mouse.
DR PRO; PR:Q99MR8; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q99MR8; protein.
DR Bgee; ENSMUSG00000027709; Expressed in brown adipose tissue and 276 other tissues.
DR ExpressionAtlas; Q99MR8; baseline and differential.
DR Genevisible; Q99MR8; MM.
DR GO; GO:0002169; C:3-methylcrotonyl-CoA carboxylase complex, mitochondrial; ISO:MGI.
DR GO; GO:1905202; C:methylcrotonoyl-CoA carboxylase complex; ISS:UniProtKB.
DR GO; GO:0005743; C:mitochondrial inner membrane; HDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR GO; GO:0004485; F:methylcrotonoyl-CoA carboxylase activity; ISO:MGI.
DR GO; GO:0006552; P:leucine catabolic process; IEA:UniProtKB-UniPathway.
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 Acetylation; ATP-binding; Biotin; Ligase; Mitochondrion;
KW Nucleotide-binding; Reference proteome; Transit peptide.
FT TRANSIT 1..38
FT /note="Mitochondrion"
FT /evidence="ECO:0000250"
FT CHAIN 39..717
FT /note="Methylcrotonoyl-CoA carboxylase subunit alpha,
FT mitochondrial"
FT /id="PRO_0000002834"
FT DOMAIN 45..490
FT /note="Biotin carboxylation"
FT DOMAIN 163..360
FT /note="ATP-grasp"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00409"
FT DOMAIN 622..711
FT /note="Biotinyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT ACT_SITE 335
FT /evidence="ECO:0000250"
FT BINDING 159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 180
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 193
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 233
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 577
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23576753"
FT MOD_RES 577
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 677
FT /note="N6-biotinyllysine"
FT /evidence="ECO:0000250, ECO:0000255|PROSITE-
FT ProRule:PRU01066"
FT CONFLICT 324
FT /note="R -> K (in Ref. 3; AAH21382)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="A -> P (in Ref. 1; AAG50244)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 717 AA; 79344 MW; F653FE7AC1E5AA90 CRC64;
MAAAALLAAV DRNQLRRVPI LLLQPREWAW KLRTMKYGTT PGGSITKVLI ANRGEIACRV
IRTAKKMGVQ SVAVYSEADR NSMHVDMADE AYSIGPAPSQ QSYLAMEKII QVAKSSAAQA
IHPGYGFLSE NMEFAELCKQ EGIIFIGPPS SAIRDMGIKS TSKSIMAAAG VPVVEGYHGK
DQSDQCLREH AGKIGYPVMI KAVRGGGGKG MRIVRSEREF QEQLESARRE AKKSFNDDAM
LIEKFVDTPR HVEVQVFGDH HGNAVYLFER DCSVQRRHQK IIEEAPAPGI NPEVRRKLGE
AAVRAAKAVK YVGAGTVEFI MDSRHNFYFM EMNTRLQVEH PVTEMITGTD LVEWQLRIAA
GEKIPLSQEE IPLQGHAFEA RIYAEDPDNN FMPGAGPLVH LSTPSADMST RIETGVRQGD
EVSVHYDPMI AKLVVWASDR QSALSKLRYC LHQYNIVGLR SNVDFLLRLS GHPEFEAGNV
HTDFIPQHHK DLLPSHSTIA KESVCQAALG LILKEKEMTS AFKLHTQDQF SPFSFSSGRR
LNISYTRNMT LRSGKSDIVI AVTYNRDGSY DMQIDNKSFR VLGDLSSEDG CTYLKSSING
VARKSKFILL DNTVHLFSME GSIEVGIPVP KYLSPVSAEG AQGGTIAPMT GTIEKVFVKA
GDRVKAGDSL MVMIAMKMEH TIKAPKDGRI KKVFFSEGAQ ANRHAPLVEF EEEESDK
