MUTA_MOUSE
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 03-AUG-2022, entry version 168.
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, 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 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. {ECO:0000250|UniProtKB:P22033}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.20 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}.
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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; 12.
DR IntAct; P16332; 1.
DR STRING; 10090.ENSMUSP00000130941; -.
DR iPTMnet; P16332; -.
DR PhosphoSitePlus; P16332; -.
DR SwissPalm; P16332; -.
DR EPD; P16332; -.
DR jPOST; P16332; -.
DR MaxQB; P16332; -.
DR PaxDb; P16332; -.
DR PeptideAtlas; P16332; -.
DR PRIDE; P16332; -.
DR ProteomicsDB; 252616; -.
DR Antibodypedia; 30809; 187 antibodies from 27 providers.
DR DNASU; 17850; -.
DR Ensembl; ENSMUST00000169611; ENSMUSP00000130941; ENSMUSG00000023921.
DR GeneID; 17850; -.
DR KEGG; mmu:17850; -.
DR UCSC; uc008coo.2; mouse.
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; PWGGSAY; -.
DR OrthoDB; 347581at2759; -.
DR PhylomeDB; P16332; -.
DR TreeFam; TF313557; -.
DR Reactome; R-MMU-71032; Propionyl-CoA catabolism.
DR Reactome; R-MMU-9759218; Cobalamin (Cbl) metabolism.
DR BioGRID-ORCS; 17850; 6 hits in 76 CRISPR screens.
DR ChiTaRS; Mut; mouse.
DR PRO; PR:P16332; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P16332; protein.
DR Bgee; ENSMUSG00000023921; Expressed in brown adipose tissue and 268 other tissues.
DR ExpressionAtlas; P16332; baseline and differential.
DR Genevisible; P16332; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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:UniProtKB-KW.
DR GO; GO:0004494; F:methylmalonyl-CoA mutase activity; IDA:UniProtKB.
DR GO; GO:0072341; F:modified amino acid binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0050667; P:homocysteine metabolic process; ISO:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0019678; P:propionate metabolic process, methylmalonyl pathway; IBA:GO_Central.
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; IPR006098; MMCoA_mutase_a_cat.
DR Pfam; PF02310; B12-binding; 1.
DR Pfam; PF01642; MM_CoA_mutase; 1.
DR SUPFAM; SSF51703; SSF51703; 1.
DR SUPFAM; SSF52242; SSF52242; 1.
DR TIGRFAMs; TIGR00640; acid_CoA_mut_C; 1.
DR TIGRFAMs; TIGR00641; acid_CoA_mut_N; 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
