ID   MUTA_MOUSE              Reviewed;         748 AA.
AC   P16332; Q3UJU1;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   04-NOV-2026, entry version 186.
DE   RecName: Full=Methylmalonyl-CoA mutase, mitochondrial;
DE            Short=MCM;
DE            EC=5.4.99.2 {ECO:0000269|PubMed:1978672};
DE   AltName: Full=Methylmalonyl-CoA isomerase;
DE   Flags: Precursor;
GN   Name=Mmut; Synonyms=Mut {ECO:0000312|MGI:MGI:97239};
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], FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND COFACTOR.
RC   TISSUE=Liver;
RX   PubMed=1978672; DOI=10.1042/bj2710449;
RA   Wilkemeyer M.F., Crane A.M., Ledley F.D.;
RT   "Primary structure and activity of mouse methylmalonyl-CoA mutase.";
RL   Biochem. J. 271:449-455(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=BALB/cJ;
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 GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Pancreas, 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   SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-341 AND LYS-593, AND
RP   IDENTIFICATION BY MASS 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   [6]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-87; LYS-210; LYS-333 AND LYS-600,
RP   AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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: Catalyzes the reversible isomerization of methylmalonyl-CoA
CC       (MMCoA) (generated from branched-chain amino acid metabolism and
CC       degradation of dietary odd chain fatty acids and cholesterol) to
CC       succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the
CC       tricarboxylic acid cycle. {ECO:0000269|PubMed:1978672}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-methylmalonyl-CoA = succinyl-CoA; Xref=Rhea:RHEA:22888,
CC         ChEBI:CHEBI:57292, ChEBI:CHEBI:57326; EC=5.4.99.2;
CC         Evidence={ECO:0000269|PubMed:1978672};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22889;
CC         Evidence={ECO:0000305|PubMed:1978672};
CC   -!- COFACTOR:
CC       Name=adenosylcob(III)alamin; Xref=ChEBI:CHEBI:18408;
CC         Evidence={ECO:0000269|PubMed:1978672};
CC   -!- ACTIVITY REGULATION: Inhibited by itaconyl-CoA, a metabolite that
CC       inactivates the coenzyme B12 cofactor. Inhibited by malyl-coA.
CC       {ECO:0000250|UniProtKB:P22033}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.2 uM for adenosylcob(III)alamin {ECO:0000269|PubMed:1978672};
CC         KM=0.27 mM for methylmalonyl-CoA {ECO:0000269|PubMed:1978672};
CC   -!- SUBUNIT: Homodimer. Interacts (the apoenzyme form) with MMAA; the
CC       interaction is GTP dependent. {ECO:0000250|UniProtKB:P22033}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000250|UniProtKB:P22033}. Mitochondrion
CC       {ECO:0000250|UniProtKB:P22033}. Cytoplasm
CC       {ECO:0000250|UniProtKB:P22033}.
CC   -!- SIMILARITY: Belongs to the methylmalonyl-CoA mutase family.
CC       {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; X51941; CAA36204.1; -; mRNA.
DR   EMBL; AK146309; BAE27064.1; -; mRNA.
DR   EMBL; CH466559; EDL23389.1; -; Genomic_DNA.
DR   CCDS; CCDS37618.1; -.
DR   PIR; S08680; S08680.
DR   RefSeq; NP_032676.2; NM_008650.3.
DR   AlphaFoldDB; P16332; -.
DR   SMR; P16332; -.
DR   BioGRID; 201624; 13.
DR   FunCoup; P16332; 1511.
DR   IntAct; P16332; 1.
DR   STRING; 10090.ENSMUSP00000130941; -.
DR   GlyCosmos; P16332; 1 site, 1 glycan.
DR   GlyGen; P16332; 2 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (1 site).
DR   iPTMnet; P16332; -.
DR   PhosphoSitePlus; P16332; -.
DR   SwissPalm; P16332; -.
DR   jPOST; P16332; -.
DR   PaxDb; 10090-ENSMUSP00000130941; -.
DR   PeptideAtlas; P16332; -.
DR   ProteomicsDB; 252616; -.
DR   Pumba; P16332; -.
DR   Antibodypedia; 30809; 265 antibodies from 30 providers.
DR   DNASU; 17850; -.
DR   Ensembl; ENSMUST00000169611.4; ENSMUSP00000130941.3; ENSMUSG00000023921.10.
DR   GeneID; 17850; -.
DR   KEGG; mmu:17850; -.
DR   UCSC; uc008coo.2; mouse.
DR   AGR; MGI:97239; -.
DR   CTD; 4594; -.
DR   MGI; MGI:97239; Mmut.
DR   VEuPathDB; HostDB:ENSMUSG00000023921; -.
DR   eggNOG; ENOG502QQ7X; Eukaryota.
DR   GeneTree; ENSGT00390000011892; -.
DR   HOGENOM; CLU_009523_3_1_1; -.
DR   InParanoid; P16332; -.
DR   OMA; AACTIMD; -.
DR   OrthoDB; 198977at2759; -.
DR   PhylomeDB; P16332; -.
DR   Reactome; R-MMU-71032; Propionyl-CoA catabolism.
DR   Reactome; R-MMU-9759218; Cobalamin (Cbl) metabolism.
DR   BioGRID-ORCS; 17850; 6 hits in 81 CRISPR screens.
DR   PRO; PR:P16332; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; P16332; protein.
DR   Bgee; ENSMUSG00000023921; Expressed in brown adipose tissue and 271 other cell types or tissues.
DR   ExpressionAtlas; P16332; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR   GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR   GO; GO:0031419; F:cobalamin binding; ISS:UniProtKB.
DR   GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:InterPro.
DR   GO; GO:0004494; F:methylmalonyl-CoA mutase activity; IDA:UniProtKB.
DR   GO; GO:0072341; F:modified amino acid binding; ISO:GO_Central.
DR   GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR   GO; GO:0050667; P:homocysteine metabolic process; ISO:GO_Central.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; ISO:GO_Central.
DR   GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR   GO; GO:1902859; P:propionyl-CoA catabolic process; IBA:GO_Central.
DR   GO; GO:1901290; P:succinyl-CoA biosynthetic process; IDA:MGI.
DR   CDD; cd02071; MM_CoA_mut_B12_BD; 1.
DR   CDD; cd03679; MM_CoA_mutase_alpha_like; 1.
DR   FunFam; 3.20.20.240:FF:000002; Methylmalonyl-CoA mutase, mitochondrial; 1.
DR   FunFam; 3.40.50.280:FF:000002; Methylmalonyl-CoA mutase, mitochondrial; 1.
DR   Gene3D; 3.40.50.280; Cobalamin-binding domain; 1.
DR   Gene3D; 3.20.20.240; Methylmalonyl-CoA mutase; 1.
DR   InterPro; IPR006159; Acid_CoA_mut_C.
DR   InterPro; IPR016176; Cbl-dep_enz_cat.
DR   InterPro; IPR006158; Cobalamin-bd.
DR   InterPro; IPR036724; Cobalamin-bd_sf.
DR   InterPro; IPR006099; MeMalonylCoA_mutase_a/b_cat.
DR   InterPro; IPR058549; MeMalonylCoA_mutase_a/b_site.
DR   InterPro; IPR006098; MMCoA_mutase_a_cat.
DR   NCBIfam; TIGR00640; acid_CoA_mut_C; 1.
DR   NCBIfam; TIGR00641; acid_CoA_mut_N; 1.
DR   NCBIfam; NF006944; scpA; 1.
DR   PANTHER; PTHR48101:SF4; METHYLMALONYL-COA MUTASE, MITOCHONDRIAL; 1.
DR   PANTHER; PTHR48101; METHYLMALONYL-COA MUTASE, MITOCHONDRIAL-RELATED; 1.
DR   Pfam; PF02310; B12-binding; 1.
DR   Pfam; PF01642; MM_CoA_mutase; 1.
DR   SUPFAM; SSF52242; Cobalamin (vitamin B12)-binding domain; 1.
DR   SUPFAM; SSF51703; Cobalamin (vitamin B12)-dependent enzymes; 1.
DR   PROSITE; PS51332; B12_BINDING; 1.
DR   PROSITE; PS00544; METMALONYL_COA_MUTASE; 1.
PE   1: Evidence at protein level;
KW   Acetylation; Cobalamin; Cobalt; Cytoplasm; Isomerase; Metal-binding;
KW   Mitochondrion; Phosphoprotein; Reference proteome; Transit peptide.
FT   TRANSIT         1..30
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   CHAIN           31..748
FT                   /note="Methylmalonyl-CoA mutase, mitochondrial"
FT                   /id="PRO_0000019295"
FT   DOMAIN          612..744
FT                   /note="B12-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00666"
FT   BINDING         48
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         94..97
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         104..108
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         214..216
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         226
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         253
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         263
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         302..304
FT                   /ligand="malonyl-CoA"
FT                   /ligand_id="ChEBI:CHEBI:57384"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   BINDING         625
FT                   /ligand="adenosylcob(III)alamin"
FT                   /ligand_id="ChEBI:CHEBI:18408"
FT                   /ligand_part="Co"
FT                   /ligand_part_id="ChEBI:CHEBI:27638"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   MOD_RES         87
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         210
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         333
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   MOD_RES         341
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         479
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P22033"
FT   MOD_RES         593
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         600
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23576753"
FT   CONFLICT        256
FT                   /note="S -> P (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        269
FT                   /note="A -> T (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        385
FT                   /note="T -> S (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        407
FT                   /note="Q -> R (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        491
FT                   /note="Q -> H (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        499..508
FT                   /note="EVLAIDNTSV -> HLLAIDIISL (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        561
FT                   /note="G -> P (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        567
FT                   /note="L -> F (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        613..614
FT                   /note="PR -> LG (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        622
FT                   /note="Q -> K (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        657..658
FT                   /note="QQ -> HD (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        672
FT                   /note="L -> H (in Ref. 1; CAA36204)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   748 AA;  82844 MW;  DF4A62100A8BD743 CRC64;
     MLRAKNQLFL LSPHYLKQLN IPSASRWKRL LHQQQPLHPE WAVLAKKQLK GKNPEDLIWH
     TPEGISIKPL YSRADTLDLP EELPGVKPFT RGPYPTMYTY RPWTIRQYAG FSTVEESNKF
     YKDNIKAGQQ GLSVAFDLAT HRGYDSDNPR VRGDVGMAGV AIDTVEDTKI LFDGIPLEKM
     SVSMTMNGAV IPVLATFIVT GEEQGVPKEK LTGTIQNDIL KEFMVRNTYI FPPEPSMKII
     ADIFQYTAQH MPKFNSISIS GYHMQEAGAD AILELAYTIA DGLEYCRTGL QAGLTIDEFA
     PRLSFFWGIG MNFYMEIAKM RAGRRLWAHL IEKMFQPKNS KSLLLRAHCQ TSGWSLTEQD
     PYNNIVRTAI EAMAAVFGGT QSLHTNSFDE ALGLPTVKSA RIARNTQIII QEESGIPKVA
     DPWGGSYMME SLTNDVYEAA LKLIYEVEEM GGMAKAVAEG IPKLRIEECA ARRQARIDSG
     SEVIVGVNKY QLEKEDSVEV LAIDNTSVRK KQIEKLKKIK SSRDQALAEQ CLSALTQCAA
     SGDGNILALA VDAARARCTV GEITDALKKV FGEHKANDRM VSGAYRQEFG ESKEITSAIK
     RVNKFMEREG RRPRLLVAKM GQDGHDRGAK VIATGFADLG FDVDIGPLFQ TPREVAQQAV
     DADVHAVGVS TLAAGHKTLV PELIKELTAL GRPDILVMCG GVIPPQDYEF LYEVGVSNVF
     GPGTRIPRAA VQVLDDIEKC LAEKQQSV
//