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Identification
HMDB Protein ID HMDBP00257
Secondary Accession Numbers
  • 5489
  • HMDBP03322
Name Methylmalonyl-CoA mutase, mitochondrial
Synonyms
  1. MCM
  2. Methylmalonyl-CoA isomerase
Gene Name MUT
Protein Type Enzyme
Biological Properties
General Function Involved in isomerase activity
Specific Function Involved in the degradation of several amino acids, odd-chain fatty acids and cholesterol via propionyl-CoA to the tricarboxylic acid cycle. MCM has different functions in other species.
Pathways
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • Beta-Ketothiolase Deficiency
  • Glyoxylate and dicarboxylate metabolism
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • Malonic Aciduria
  • Malonyl-coa decarboxylase deficiency
  • Maple Syrup Urine Disease
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • Methylmalonic Aciduria Due to Cobalamin-Related Disorders
  • Propanoate Metabolism
  • Propanoate metabolism
  • Propionic Acidemia
  • Threonine and 2-Oxobutanoate Degradation
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
Reactions
Methylmalonyl-CoA → Succinyl-CoA details
GO Classification
Biological Process
short-chain fatty acid catabolic process
homocysteine metabolic process
post-embryonic development
fatty acid beta-oxidation
Cellular Component
mitochondrial matrix
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
cobalamin binding
vitamin binding
isomerase activity
methylmalonyl-coa mutase activity
intramolecular transferase activity
Molecular Function
metal ion binding
methylmalonyl-CoA mutase activity
cobalamin binding
modified amino acid binding
Process
metabolic process
Cellular Location
  1. Mitochondrion matrix
Gene Properties
Chromosome Location 6
Locus 6p12.3
SNPs MUT
Gene Sequence
>2253 bp
ATGTTAAGAGCTAAGAATCAGCTTTTTTTACTTTCACCTCATTACCTGAGGCAGGTAAAA
GAATCATCAGGCTCCAGGCTCATACAGCAACGACTTCTACACCAGCAACAGCCCCTTCAC
CCAGAATGGGCTGCCCTGGCTAAAAAGCAGCTGAAAGGCAAAAACCCAGAAGACCTAATA
TGGCACACCCCGGAAGGGATCTCTATAAAACCCTTGTATTCCAAGAGAGATACTATGGAC
TTACCTGAAGAACTTCCAGGAGTGAAGCCATTCACACGTGGACCATATCCTACCATGTAT
ACCTTTAGGCCCTGGACCATCCGCCAGTATGCTGGTTTTAGTACTGTGGAAGAAAGCAAT
AAGTTCTATAAGGACAACATTAAGGCTGGTCAGCAGGGATTATCAGTTGCCTTTGATCTG
GCGACACATCGTGGCTATGATTCAGACAACCCTCGAGTTCGTGGTGATGTTGGAATGGCT
GGAGTTGCTATTGACACTGTGGAAGATACCAAAATTCTTTTTGATGGAATTCCTTTAGAA
AAAATGTCAGTTTCCATGACTATGAATGGAGCAGTTATTCCAGTTCTTGCAAATTTTATA
GTAACTGGAGAAGAACAAGGTGTACCTAAAGAGAAACTTACTGGTACCATCCAAAATGAT
ATACTAAAGGAATTTATGGTTCGAAATACATACATTTTTCCTCCAGAACCATCCATGAAA
ATTATTGCTGACATATTTGAATATACAGCAAAGCACATGCCAAAATTTAATTCAATTTCA
ATTAGTGGATACCATATGCAGGAAGCAGGGGCTGATGCCATTCTGGAGCTGGCCTATACT
TTAGCAGATGGATTGGAGTACTCTAGAACTGGACTCCAGGCTGGCCTGACAATTGATGAA
TTTGCACCAAGGTTGTCTTTCTTCTGGGGAATTGGAATGAATTTCTATATGGAAATAGCA
AAGATGAGAGCTGGTAGAAGACTCTGGGCTCACTTAATAGAGAAAATGTTTCAGCCTAAA
AACTCAAAATCTCTTCTTCTAAGAGCACACTGTCAGACATCTGGATGGTCACTTACTGAG
CAGGATCCCTACAATAATATTGTCCGTACTGCAATAGAAGCAATGGCAGCAGTATTTGGA
GGGACTCAGTCTTTGCACACAAATTCTTTTGATGAAGCTTTGGGTTTGCCAACTGTGAAA
AGTGCTCGAATTGCCAGGAACACACAAATCATCATTCAAGAAGAATCTGGGATTCCCAAA
GTGGCTGATCCTTGGGGAGGTTCTTACATGATGGAATGTCTCACAAATGATGTTTATGAT
GCTGCTTTAAAGCTCATTAATGAAATTGAAGAAATGGGTGGAATGGCCAAAGCTGTAGCT
GAGGGAATACCTAAACTTCGAATTGAAGAATGTGCTGCCCGAAGACAAGCTAGAATAGAT
TCTGGTTCTGAAGTAATTGTTGGAGTAAATAAGTACCAGTTGGAAAAAGAAGACGCTGTA
GAAGTTCTGGCAATTGATAATACTTCAGTGCGAAACAGGCAGATTGAAAAACTTAAGAAG
ATCAAATCCAGCAGGGATCAAGCTTTGGCTGAACATTGTCTTGCTGCACTAACCGAATGT
GCTGCTAGCGGAGATGGAAATATCCTGGCTCTTGCAGTGGATGCATCTCGGGCAAGATGT
ACAGTGGGAGAAATCACAGATGCCCTGAAAAAGGTATTTGGTGAACATAAAGCGAATGAT
CGAATGGTGAGTGGAGCATATCGCCAGGAATTTGGAGAAAGTAAAGAGATAACATCTGCT
ATCAAGAGGGTTCATAAATTCATGGAACGTGAAGGTCGCAGACCTCGTCTTCTTGTAGCA
AAAATGGGACAAGATGGCCATGACAGAGGAGCAAAAGTTATTGCTACAGGATTTGCTGAT
CTTGGTTTTGATGTGGACATAGGCCCTCTTTTCCAGACTCCTCGTGAAGTGGCCCAGCAG
GCTGTGGATGCGGATGTGCATGCTGTGGGCGTAAGCACCCTCGCTGCTGGTCATAAAACC
CTAGTTCCTGAACTCATCAAAGAACTTAACTCCCTTGGACGGCCAGATATTCTTGTCATG
TGTGGAGGGGTGATACCACCTCAGGATTATGAATTTCTGTTTGAAGTTGGTGTTTCCAAT
GTATTTGGTCCTGGGACTCGAATTCCAAAGGCTGCCGTTCAGGTGCTTGATGATATTGAG
AAGTGTTTGGAAAAGAAGCAGCAATCTGTATAA
Protein Properties
Number of Residues 750
Molecular Weight 83133.755
Theoretical pI 6.93
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Methylmalonyl-CoA mutase, mitochondrial
MLRAKNQLFLLSPHYLRQVKESSGSRLIQQRLLHQQQPLHPEWAALAKKQLKGKNPEDLI
WHTPEGISIKPLYSKRDTMDLPEELPGVKPFTRGPYPTMYTFRPWTIRQYAGFSTVEESN
KFYKDNIKAGQQGLSVAFDLATHRGYDSDNPRVRGDVGMAGVAIDTVEDTKILFDGIPLE
KMSVSMTMNGAVIPVLANFIVTGEEQGVPKEKLTGTIQNDILKEFMVRNTYIFPPEPSMK
IIADIFEYTAKHMPKFNSISISGYHMQEAGADAILELAYTLADGLEYSRTGLQAGLTIDE
FAPRLSFFWGIGMNFYMEIAKMRAGRRLWAHLIEKMFQPKNSKSLLLRAHCQTSGWSLTE
QDPYNNIVRTAIEAMAAVFGGTQSLHTNSFDEALGLPTVKSARIARNTQIIIQEESGIPK
VADPWGGSYMMECLTNDVYDAALKLINEIEEMGGMAKAVAEGIPKLRIEECAARRQARID
SGSEVIVGVNKYQLEKEDAVEVLAIDNTSVRNRQIEKLKKIKSSRDQALAERCLAALTEC
AASGDGNILALAVDASRARCTVGEITDALKKVFGEHKANDRMVSGAYRQEFGESKEITSA
IKRVHKFMEREGRRPRLLVAKMGQDGHDRGAKVIATGFADLGFDVDIGPLFQTPREVAQQ
AVDADVHAVGVSTLAAGHKTLVPELIKELNSLGRPDILVMCGGVIPPQDYEFLFEVGVSN
VFGPGTRIPKAAVQVLDDIEKCLEKKQQSV
GenBank ID Protein 187452
UniProtKB/Swiss-Prot ID P22033
UniProtKB/Swiss-Prot Entry Name MUTA_HUMAN
PDB IDs
GenBank Gene ID M65131
GeneCard ID MUT
GenAtlas ID MUT
HGNC ID HGNC:7526
References
General References
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  4. Jansen R, Kalousek F, Fenton WA, Rosenberg LE, Ledley FD: Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction. Genomics. 1989 Feb;4(2):198-205. [PubMed:2567699 ]
  5. Nham SU, Wilkemeyer MF, Ledley FD: Structure of the human methylmalonyl-CoA mutase (MUT) locus. Genomics. 1990 Dec;8(4):710-6. [PubMed:1980486 ]
  6. Jansen R, Ledley FD: Heterozygous mutations at the mut locus in fibroblasts with mut0 methylmalonic acidemia identified by polymerase-chain-reaction cDNA cloning. Am J Hum Genet. 1990 Nov;47(5):808-14. [PubMed:1977311 ]
  7. Raff ML, Crane AM, Jansen R, Ledley FD, Rosenblatt DS: Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation. J Clin Invest. 1991 Jan;87(1):203-7. [PubMed:1670635 ]
  8. Crane AM, Martin LS, Valle D, Ledley FD: Phenotype of disease in three patients with identical mutations in methylmalonyl CoA mutase. Hum Genet. 1992 May;89(3):259-64. [PubMed:1351030 ]
  9. Crane AM, Jansen R, Andrews ER, Ledley FD: Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria. J Clin Invest. 1992 Feb;89(2):385-91. [PubMed:1346616 ]
  10. Crane AM, Ledley FD: Clustering of mutations in methylmalonyl CoA mutase associated with mut- methylmalonic acidemia. Am J Hum Genet. 1994 Jul;55(1):42-50. [PubMed:7912889 ]
  11. Qureshi AA, Crane AM, Matiaszuk NV, Rezvani I, Ledley FD, Rosenblatt DS: Cloning and expression of mutations demonstrating intragenic complementation in mut0 methylmalonic aciduria. J Clin Invest. 1994 Apr;93(4):1812-9. [PubMed:7909321 ]
  12. Janata J, Kogekar N, Fenton WA: Expression and kinetic characterization of methylmalonyl-CoA mutase from patients with the mut- phenotype: evidence for naturally occurring interallelic complementation. Hum Mol Genet. 1997 Sep;6(9):1457-64. [PubMed:9285782 ]
  13. Ledley FD, Rosenblatt DS: Mutations in mut methylmalonic acidemia: clinical and enzymatic correlations. Hum Mutat. 1997;9(1):1-6. [PubMed:8990001 ]
  14. Adjalla CE, Hosack AR, Matiaszuk NV, Rosenblatt DS: A common mutation among blacks with mut- methylmalonic aciduria. Hum Mutat. 1998;Suppl 1:S248-50. [PubMed:9452100 ]
  15. Adjalla CE, Hosack AR, Gilfix BM, Lamothe E, Sun S, Chan A, Evans S, Matiaszuk NV, Rosenblatt DS: Seven novel mutations in mut methylmalonic aciduria. Hum Mutat. 1998;11(4):270-4. [PubMed:9554742 ]
  16. Fuchshuber A, Mucha B, Baumgartner ER, Vollmer M, Hildebrandt F: mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA mutase including a deletion-insertion mutation. Hum Mutat. 2000 Aug;16(2):179. [PubMed:10923046 ]
  17. Berger I, Shaag A, Anikster Y, Baumgartner ER, Bar-Meir M, Joseph A, Elpeleg ON: Mutation analysis of the MCM gene in Israeli patients with mut(0) disease. Mol Genet Metab. 2001 May;73(1):107-10. [PubMed:11350191 ]
  18. Acquaviva C, Benoist JF, Pereira S, Callebaut I, Koskas T, Porquet D, Elion J: Molecular basis of methylmalonyl-CoA mutase apoenzyme defect in 40 European patients affected by mut(o) and mut- forms of methylmalonic acidemia: identification of 29 novel mutations in the MUT gene. Hum Mutat. 2005 Feb;25(2):167-76. [PubMed:15643616 ]
  19. Martinez MA, Rincon A, Desviat LR, Merinero B, Ugarte M, Perez B: Genetic analysis of three genes causing isolated methylmalonic acidemia: identification of 21 novel allelic variants. Mol Genet Metab. 2005 Apr;84(4):317-25. Epub 2005 Jan 22. [PubMed:15781192 ]
  20. Worgan LC, Niles K, Tirone JC, Hofmann A, Verner A, Sammak A, Kucic T, Lepage P, Rosenblatt DS: Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006 Jan;27(1):31-43. [PubMed:16281286 ]