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Protein

Methylmalonyl-CoA mutase, mitochondrial

Gene

MUT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.

Catalytic activityi

(R)-methylmalonyl-CoA = succinyl-CoA.2 Publications

Cofactori

adenosylcob(III)alamin1 Publication

Activity regulationi

Inhibited by itaconyl-CoA, a metabolite that inactivates the coenzyme B12 cofactor (PubMed:29056341).

Kineticsi

  1. KM=4.7 nM for adenosylcob(III)alamin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei50malonyl-CoA1 Publication1
    Binding sitei228malonyl-CoA1 Publication1
    Binding sitei255malonyl-CoA1 Publication1
    Binding sitei265malonyl-CoA1 Publication1
    Metal bindingi627Cobalt (cobalamin 2 axial ligand)1 Publication1

    GO - Molecular functioni

    • cobalamin binding Source: UniProtKB
    • GTPase activity Source: UniProtKB
    • identical protein binding Source: UniProtKB
    • metal ion binding Source: UniProtKB-KW
    • methylmalonyl-CoA mutase activity Source: UniProtKB
    • modified amino acid binding Source: UniProtKB
    • protein homodimerization activity Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionIsomerase
    LigandCobalamin, Cobalt, Metal-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS07322-MONOMER
    BRENDAi5.4.99.2 2681
    ReactomeiR-HSA-196741 Cobalamin (Cbl, vitamin B12) transport and metabolism
    R-HSA-3359475 Defective MMAA causes methylmalonic aciduria type cblA
    R-HSA-3359478 Defective MUT causes methylmalonic aciduria mut type
    R-HSA-71032 Propionyl-CoA catabolism
    SABIO-RKiP22033

    Chemistry databases

    SwissLipidsiSLP:000001254

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Methylmalonyl-CoA mutase, mitochondrial (EC:5.4.99.22 Publications)
    Short name:
    MCM
    Alternative name(s):
    Methylmalonyl-CoA isomerase
    Gene namesi
    Name:MUTImported
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000146085.7
    HGNCiHGNC:7526 MUT
    MIMi609058 gene
    neXtProtiNX_P22033

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Methylmalonic aciduria type mut (MMAM)23 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAn often fatal disorder of organic acid metabolism. Common clinical features include lethargy, vomiting, failure to thrive, hypotonia, neurological deficit and early death. Two forms of the disease are distinguished by the presence (mut-) or absence (mut0) of residual enzyme activity. Mut0 patients have more severe neurological manifestations of the disease than do MUT- patients. MMAM is unresponsive to vitamin B12 therapy.
    See also OMIM:251000
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0800317 – 750Missing in MMAM; mut-. 1 PublicationAdd BLAST744
    Natural variantiVAR_02347269I → V in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs115923556EnsemblClinVar.1
    Natural variantiVAR_02659286P → L in MMAM; mut0 and mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs769348060EnsemblClinVar.1
    Natural variantiVAR_02659387G → E in MMAM; mut0. 1 Publication1
    Natural variantiVAR_00440993R → H in MMAM; mut0; decreased methylmalonyl-CoA mutase activity. 4 PublicationsCorresponds to variant dbSNP:rs121918251EnsemblClinVar.1
    Natural variantiVAR_02659494G → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs727504022EnsemblClinVar.1
    Natural variantiVAR_02239394G → V in MMAM; mut- and mut0. 2 PublicationsCorresponds to variant dbSNP:rs535411418Ensembl.1
    Natural variantiVAR_02659595P → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs190834116EnsemblClinVar.1
    Natural variantiVAR_075379100Y → C in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs864309735EnsemblClinVar.1
    Natural variantiVAR_004410105W → R in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs121918249EnsemblClinVar.1
    Natural variantiVAR_026596108R → C in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs121918257EnsemblClinVar.1
    Natural variantiVAR_026597108R → G in MMAM; mut-. 1 Publication1
    Natural variantiVAR_022394108R → H in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs483352778EnsemblClinVar.1
    Natural variantiVAR_023473109Q → R in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs1461110052Ensembl.1
    Natural variantiVAR_075380110Y → C in MMAM. 1 PublicationCorresponds to variant dbSNP:rs796052005EnsemblClinVar.1
    Natural variantiVAR_077210126N → K in MMAM. 1 PublicationCorresponds to variant dbSNP:rs879253827EnsemblClinVar.1
    Natural variantiVAR_077211133G → R in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs879253828EnsemblClinVar.1
    Natural variantiVAR_075381137A → G in MMAM. 1 PublicationCorresponds to variant dbSNP:rs941483851EnsemblClinVar.1
    Natural variantiVAR_022395137A → V in MMAM; mut0. 2 Publications1
    Natural variantiVAR_077212139D → N in MMAM; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879253829EnsemblClinVar.1
    Natural variantiVAR_078342140L → P in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity. 2 Publications1
    Natural variantiVAR_078343141A → T in MMAM; decreased protein expression. 1 Publication1
    Natural variantiVAR_075382143H → Y in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026598145G → S in MMAM; mut0. 1 Publication1
    Natural variantiVAR_022396148S → L in MMAM; mut0. 2 Publications1
    Natural variantiVAR_080032152 – 750Missing in MMAM; mut0. 1 PublicationAdd BLAST599
    Natural variantiVAR_022397156D → N in MMAM; mut-. 1 Publication1
    Natural variantiVAR_077213156D → V in MMAM. 1 PublicationCorresponds to variant dbSNP:rs757000253EnsemblClinVar.1
    Natural variantiVAR_022398158G → V in MMAM; mut0. 1 Publication1
    Natural variantiVAR_077214161G → R in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 2 Publications1
    Natural variantiVAR_078344161G → V in MMAM; decreased protein expression. 1 Publication1
    Natural variantiVAR_022399174F → S in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs864309733EnsemblClinVar.1
    Natural variantiVAR_026599186M → V in MMAM; mut-. 1 PublicationCorresponds to variant dbSNP:rs148331800EnsemblClinVar.1
    Natural variantiVAR_077215187T → S in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs879253830EnsemblClinVar.1
    Natural variantiVAR_077216189N → I in MMAM; mut-; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs200908035EnsemblClinVar.1
    Natural variantiVAR_026600189N → K in MMAM; mut-. 1 Publication1
    Natural variantiVAR_004411191A → E in MMAM; mut- and mut0; affects proper folding; reduced protein level; decreased methylmalonyl-CoA mutase activity. 8 PublicationsCorresponds to variant dbSNP:rs760782399EnsemblClinVar.1
    Natural variantiVAR_026601197A → E in MMAM; mut0. 1 Publication1
    Natural variantiVAR_022400203G → R in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 6 PublicationsCorresponds to variant dbSNP:rs778702777EnsemblClinVar.1
    Natural variantiVAR_077217205Missing in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026602215G → C in MMAM; mut- and mut0. 1 Publication1
    Natural variantiVAR_022401215G → S in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs121918258EnsemblClinVar.1
    Natural variantiVAR_022402218Q → H in MMAM; mut0 and mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; alters thermodynamic stability. 4 Publications1
    Natural variantiVAR_022403219N → Y in MMAM; mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity. 8 PublicationsCorresponds to variant dbSNP:rs121918256EnsemblClinVar.1
    Natural variantiVAR_080033228 – 750Missing in MMAM; mut0. 1 PublicationAdd BLAST523
    Natural variantiVAR_004412228R → Q in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs770810987Ensembl.1
    Natural variantiVAR_026603230T → I in MMAM; mut-. 1 Publication1
    Natural variantiVAR_077218230T → R in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs879253833EnsemblClinVar.1
    Natural variantiVAR_004413231Y → N in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 5 PublicationsCorresponds to variant dbSNP:rs864309736EnsemblClinVar.1
    Natural variantiVAR_022404262S → N in MMAM; mut0. 2 Publications1
    Natural variantiVAR_026604265H → Y in MMAM; mut-. 1 Publication1
    Natural variantiVAR_077219276E → D in MMAM; mut-; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs12175488EnsemblClinVar.1
    Natural variantiVAR_026605281L → S in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs796052007EnsemblClinVar.1
    Natural variantiVAR_077220284G → E in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs879253835EnsemblClinVar.1
    Natural variantiVAR_077221284G → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs761477436EnsemblClinVar.1
    Natural variantiVAR_075383288S → P in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 2 Publications1
    Natural variantiVAR_026606291G → E in MMAM; mut0. 1 Publication1
    Natural variantiVAR_022405293Q → P in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026607305L → S in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 3 Publications1
    Natural variantiVAR_026608306S → F in MMAM; mut0. 1 Publication1
    Natural variantiVAR_078345309W → G in MMAM; decreased protein expression. 1 Publication1
    Natural variantiVAR_004414312G → V in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs864309734EnsemblClinVar.1
    Natural variantiVAR_026609316Y → C in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; no decreased affinity for adenosylcob(III)alamin. 2 PublicationsCorresponds to variant dbSNP:rs781474200Ensembl.1
    Natural variantiVAR_023474324A → T in MMAM; mut-. 3 Publications1
    Natural variantiVAR_077222325G → D in MMAM. 1 PublicationCorresponds to variant dbSNP:rs879253837EnsemblClinVar.1
    Natural variantiVAR_077223326R → K in MMAM; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs758577372EnsemblClinVar.1
    Natural variantiVAR_022406328L → F in MMAM; mut0; affects proper folding; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity. 4 PublicationsCorresponds to variant dbSNP:rs796052002EnsemblClinVar.1
    Natural variantiVAR_023475328L → P in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs965316043EnsemblClinVar.1
    Natural variantiVAR_075384344S → F in MMAM; mut-; affects proper folding; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin. 2 Publications1
    Natural variantiVAR_004415346Missing in MMAM; mut0. 2 Publications1
    Natural variantiVAR_026610347L → R in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026611350H → Y in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs1407914109Ensembl.1
    Natural variantiVAR_077224358L → P in MMAM; mut0. 1 Publication1
    Natural variantiVAR_075385364Y → S in MMAM. 1 PublicationCorresponds to variant dbSNP:rs563776413Ensembl.1
    Natural variantiVAR_075386366N → S in MMAM; mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs864309737EnsemblClinVar.1
    Natural variantiVAR_004416368V → D in MMAM. 1
    Natural variantiVAR_026612369R → C in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs772552898EnsemblClinVar.1
    Natural variantiVAR_004417369R → H in MMAM; mut- and mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; alters thermodynamic stability. 4 PublicationsCorresponds to variant dbSNP:rs564069299EnsemblClinVar.1
    Natural variantiVAR_026613370T → P in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs368790885EnsemblClinVar.1
    Natural variantiVAR_004418377A → E in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 3 PublicationsCorresponds to variant dbSNP:rs121918250EnsemblClinVar.1
    Natural variantiVAR_026614383Q → H in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026615383Q → P in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026616386H → N in MMAM; mut0. 1 Publication1
    Natural variantiVAR_077225386H → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs866933356Ensembl.1
    Natural variantiVAR_075387387T → I in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 3 Publications1
    Natural variantiVAR_026617388N → H in MMAM; mut0. 1 Publication1
    Natural variantiVAR_077226388N → K in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs879253840EnsemblClinVar.1
    Natural variantiVAR_026618389Missing in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026619412Missing in MMAM; mut0. 1 Publication1
    Natural variantiVAR_077227424P → L in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs879253842EnsemblClinVar.1
    Natural variantiVAR_077228426G → E in MMAM; mut-; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs533755473EnsemblClinVar.1
    Natural variantiVAR_026620426G → R in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs769922244Ensembl.1
    Natural variantiVAR_026621427G → D in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs753288303EnsemblClinVar.1
    Natural variantiVAR_075388454G → E in MMAM; mut0. 2 Publications1
    Natural variantiVAR_078346505I → T in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity. 1 Publication1
    Natural variantiVAR_075389514Q → E in MMAM; unknown pathological significance. 1 Publication1
    Natural variantiVAR_078347514Q → K in MMAM; decreased protein expression. 1 Publication1
    Natural variantiVAR_026622518L → P in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs864309738EnsemblClinVar.1
    Natural variantiVAR_022408535A → P in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs760183775Ensembl.1
    Natural variantiVAR_077229552A → V in MMAM; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs879253845EnsemblClinVar.1
    Natural variantiVAR_026623560C → Y in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026624566T → R in MMAM; mut0. 1 Publication1
    Natural variantiVAR_026625573F → S in MMAM; mut-; affects proper folding; no effect on protein abundance; no effect on methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; does not alter thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs775593146EnsemblClinVar.1
    Natural variantiVAR_022409587Y → C in MMAM; mut-. 1 Publication1
    Natural variantiVAR_078348597I → R in MMAM; no changed in protein expression; decreased methylmalonyl-CoA mutase activity. 1 Publication1
    Natural variantiVAR_075390615P → L in MMAM; mut0; affects proper folding; reduced strongly protein level. 3 Publications1
    Natural variantiVAR_026626615P → R in MMAM; mut0. 1 Publication1
    Natural variantiVAR_022410615P → T in MMAM; mut0; affects proper folding; reduced strongly protein level; loss of methylmalonyl-CoA mutase activity. 5 Publications1
    Natural variantiVAR_023476616R → C in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs765284825EnsemblClinVar.1
    Natural variantiVAR_023477617L → R in MMAM; mut0. 2 Publications1
    Natural variantiVAR_077230618L → P in MMAM. 1 PublicationCorresponds to variant dbSNP:rs879253846EnsemblClinVar.1
    Natural variantiVAR_022411621K → N in MMAM; mut0. 1 Publication1
    Natural variantiVAR_004420623G → R in MMAM; mut0. 4 PublicationsCorresponds to variant dbSNP:rs121918254EnsemblClinVar.1
    Natural variantiVAR_022412624Q → R in MMAM; no effect on protein abundance. 2 PublicationsCorresponds to variant dbSNP:rs768521956Ensembl.1
    Natural variantiVAR_077231625D → G in MMAM; mut0; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs879253847EnsemblClinVar.1
    Natural variantiVAR_075391625D → V in MMAM; mut0; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity. 2 Publications1
    Natural variantiVAR_004421626G → C in MMAM; mut-. 1 PublicationCorresponds to variant dbSNP:rs982110849Ensembl.1
    Natural variantiVAR_022413627H → R in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs372486357EnsemblClinVar.1
    Natural variantiVAR_004422630G → E in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs143023066EnsemblClinVar.1
    Natural variantiVAR_004423633V → G in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; does not alter thermodynamic stability. 4 PublicationsCorresponds to variant dbSNP:rs200055428EnsemblClinVar.1
    Natural variantiVAR_022414637G → E in MMAM; mut-. 1 Publication1
    Natural variantiVAR_026627637G → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs781501004Ensembl.1
    Natural variantiVAR_022415638F → I in MMAM; mut0. 1 Publication1
    Natural variantiVAR_022416640D → Y in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs865815395Ensembl.1
    Natural variantiVAR_022417642G → R in MMAM; mut-. 2 PublicationsCorresponds to variant dbSNP:rs747897332EnsemblClinVar.1
    Natural variantiVAR_004424648G → D in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs766721811Ensembl.1
    Natural variantiVAR_004425669V → E in MMAM; mut0. 1
    Natural variantiVAR_075392674L → F in MMAM; decreased protein abundance; decreased methylmalonyl-CoA mutase activity. 2 PublicationsCorresponds to variant dbSNP:rs1164271240Ensembl.1
    Natural variantiVAR_004427678H → R in MMAM; mut-. 2 PublicationsCorresponds to variant dbSNP:rs147094927Ensembl.1
    Natural variantiVAR_004428684E → EL in MMAM; mut-. 1 Publication1
    Natural variantiVAR_004429685L → R in MMAM; mut-. 2 PublicationsCorresponds to variant dbSNP:rs864309739EnsemblClinVar.1
    Natural variantiVAR_075393692L → P in MMAM. 1 Publication1
    Natural variantiVAR_075394694R → L in MMAM; mut-; decreased protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 3 Publications1
    Natural variantiVAR_004430694R → W in MMAM; mut- and mut0; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 8 PublicationsCorresponds to variant dbSNP:rs777758903EnsemblClinVar.1
    Natural variantiVAR_022418700M → K in MMAM; mut-; no effect on protein abundance; loss of methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 4 PublicationsCorresponds to variant dbSNP:rs140600746EnsemblClinVar.1
    Natural variantiVAR_004431703G → R in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs121918255EnsemblClinVar.1
    Natural variantiVAR_004432717G → V in MMAM; mut-; no effect on protein abundance; interfers with the binding of the cofactor to the apoenzyme; decreased methylmalonyl-CoA mutase activity; strong decreased affinity for adenosylcob(III)alamin; decreased thermodynamic stability. 6 PublicationsCorresponds to variant dbSNP:rs121918252EnsemblClinVar.1
    Natural variantiVAR_078349723G → D in MMAM; decreased protein expression; decreased methylmalonyl-CoA mutase activity. 1 PublicationCorresponds to variant dbSNP:rs755077681Ensembl.1
    Natural variantiVAR_077232736L → F in MMAM. 1 PublicationCorresponds to variant dbSNP:rs753461919EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi4594
    GeneReviewsiMUT
    MalaCardsiMUT
    MIMi251000 phenotype
    OpenTargetsiENSG00000146085
    Orphaneti79312 Vitamin B12-unresponsive methylmalonic acidemia type mut-
    289916 Vitamin B12-unresponsive methylmalonic acidemia type mut0
    PharmGKBiPA31327

    Chemistry databases

    DrugBankiDB00115 Cyanocobalamin
    DB00200 Hydroxocobalamin

    Polymorphism and mutation databases

    BioMutaiMUT
    DMDMi317373575

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Transit peptidei1 – 32MitochondrionAdd BLAST32
    ChainiPRO_000001929333 – 750Methylmalonyl-CoA mutase, mitochondrialAdd BLAST718

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei89N6-acetyllysineBy similarity1
    Modified residuei212N6-acetyllysineBy similarity1
    Modified residuei335N6-acetyllysineBy similarity1
    Modified residuei343N6-succinyllysineBy similarity1
    Modified residuei481PhosphoserineCombined sources1
    Modified residuei595N6-succinyllysineBy similarity1
    Modified residuei602N6-acetyllysineBy similarity1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP22033
    MaxQBiP22033
    PaxDbiP22033
    PeptideAtlasiP22033
    PRIDEiP22033
    ProteomicsDBi53953

    PTM databases

    iPTMnetiP22033
    PhosphoSitePlusiP22033

    Expressioni

    Gene expression databases

    BgeeiENSG00000146085 Expressed in 232 organ(s), highest expression level in liver
    CleanExiHS_MUT
    ExpressionAtlasiP22033 baseline and differential
    GenevisibleiP22033 HS

    Organism-specific databases

    HPAiHPA035971
    HPA035972

    Interactioni

    Subunit structurei

    Homodimer (PubMed:20876572). Interacts (the apoenzyme form) with MMAA; the interaction is GTP dependent (PubMed:20876572).1 Publication

    GO - Molecular functioni

    Protein-protein interaction databases

    BioGridi110680, 14 interactors
    IntActiP22033, 5 interactors
    MINTiP22033
    STRINGi9606.ENSP00000274813

    Structurei

    Secondary structure

    1750
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliP22033
    SMRiP22033
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP22033

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini614 – 746B12-bindingPROSITE-ProRule annotationAdd BLAST133

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni96 – 99malonyl-CoA binding1 Publication4
    Regioni106 – 110malonyl-CoA binding1 Publication5
    Regioni216 – 218malonyl-CoA binding1 Publication3
    Regioni304 – 306malonyl-CoA binding1 Publication3

    Sequence similaritiesi

    Belongs to the methylmalonyl-CoA mutase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiENOG410IE7I Eukaryota
    COG1884 LUCA
    COG2185 LUCA
    GeneTreeiENSGT00390000011892
    HOGENOMiHOG000003917
    HOVERGENiHBG006423
    InParanoidiP22033
    KOiK01847
    OMAiDRMSVSM
    OrthoDBiEOG091G02GM
    PhylomeDBiP22033
    TreeFamiTF313557

    Family and domain databases

    InterProiView protein in InterPro
    IPR006159 Acid_CoA_mut_C
    IPR016176 Cbl-dep_enz_cat
    IPR006158 Cobalamin-bd
    IPR036724 Cobalamin-bd_sf
    IPR006099 MeMalonylCoA_mutase_a/b_cat
    IPR006098 MMCoA_mutase_a_cat
    PfamiView protein in Pfam
    PF02310 B12-binding, 1 hit
    PF01642 MM_CoA_mutase, 1 hit
    SUPFAMiSSF51703 SSF51703, 1 hit
    SSF52242 SSF52242, 1 hit
    TIGRFAMsiTIGR00640 acid_CoA_mut_C, 1 hit
    TIGR00641 acid_CoA_mut_N, 1 hit
    PROSITEiView protein in PROSITE
    PS51332 B12_BINDING, 1 hit
    PS00544 METMALONYL_COA_MUTASE, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P22033-1 [UniParc]FASTAAdd to basket
    « Hide
            10         20         30         40         50
    MLRAKNQLFL LSPHYLRQVK ESSGSRLIQQ RLLHQQQPLH PEWAALAKKQ
    60 70 80 90 100
    LKGKNPEDLI WHTPEGISIK PLYSKRDTMD LPEELPGVKP FTRGPYPTMY
    110 120 130 140 150
    TFRPWTIRQY AGFSTVEESN KFYKDNIKAG QQGLSVAFDL ATHRGYDSDN
    160 170 180 190 200
    PRVRGDVGMA GVAIDTVEDT KILFDGIPLE KMSVSMTMNG AVIPVLANFI
    210 220 230 240 250
    VTGEEQGVPK EKLTGTIQND ILKEFMVRNT YIFPPEPSMK IIADIFEYTA
    260 270 280 290 300
    KHMPKFNSIS ISGYHMQEAG ADAILELAYT LADGLEYSRT GLQAGLTIDE
    310 320 330 340 350
    FAPRLSFFWG IGMNFYMEIA KMRAGRRLWA HLIEKMFQPK NSKSLLLRAH
    360 370 380 390 400
    CQTSGWSLTE QDPYNNIVRT AIEAMAAVFG GTQSLHTNSF DEALGLPTVK
    410 420 430 440 450
    SARIARNTQI IIQEESGIPK VADPWGGSYM MECLTNDVYD AALKLINEIE
    460 470 480 490 500
    EMGGMAKAVA EGIPKLRIEE CAARRQARID SGSEVIVGVN KYQLEKEDAV
    510 520 530 540 550
    EVLAIDNTSV RNRQIEKLKK IKSSRDQALA ERCLAALTEC AASGDGNILA
    560 570 580 590 600
    LAVDASRARC TVGEITDALK KVFGEHKAND RMVSGAYRQE FGESKEITSA
    610 620 630 640 650
    IKRVHKFMER EGRRPRLLVA KMGQDGHDRG AKVIATGFAD LGFDVDIGPL
    660 670 680 690 700
    FQTPREVAQQ AVDADVHAVG ISTLAAGHKT LVPELIKELN SLGRPDILVM
    710 720 730 740 750
    CGGVIPPQDY EFLFEVGVSN VFGPGTRIPK AAVQVLDDIE KCLEKKQQSV
    Length:750
    Mass (Da):83,134
    Last modified:January 11, 2011 - v4
    Checksum:iB5909729C08B562F
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti153V → L in AAA99226 (PubMed:1980486).Curated1
    Sequence conflicti236E → D in AAA99226 (PubMed:1980486).Curated1
    Sequence conflicti274 – 277ILEL → FWSW in AAA99226 (PubMed:1980486).Curated4
    Sequence conflicti316Y → H in AAA99226 (PubMed:1980486).Curated1
    Sequence conflicti516E → G in AAA99226 (PubMed:1980486).Curated1
    Sequence conflicti591F → Y in AAA99226 (PubMed:1980486).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_0800317 – 750Missing in MMAM; mut-. 1 PublicationAdd BLAST744
    Natural variantiVAR_02347269I → V in MMAM; mut0. 3 PublicationsCorresponds to variant dbSNP:rs115923556EnsemblClinVar.1
    Natural variantiVAR_02659286P → L in MMAM; mut0 and mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs769348060EnsemblClinVar.1
    Natural variantiVAR_02659387G → E in MMAM; mut0. 1 Publication1
    Natural variantiVAR_00440993R → H in MMAM; mut0; decreased methylmalonyl-CoA mutase activity. 4 PublicationsCorresponds to variant dbSNP:rs121918251EnsemblClinVar.1
    Natural variantiVAR_02659494G → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs727504022EnsemblClinVar.1
    Natural variantiVAR_02239394G → V in MMAM; mut- and mut0. 2 PublicationsCorresponds to variant dbSNP:rs535411418Ensembl.1
    Natural variantiVAR_02659595P → R in MMAM; mut0. 1 PublicationCorresponds to variant dbSNP:rs190834116EnsemblClinVar.1
    Natural variantiVAR_075379100Y → C in MMAM; mut-; no effect on protein abundance; decreased methylmalonyl-CoA mutase activity; decreased affinity for adenosylcob(III)alamin; alters thermodynamic stability. 2 PublicationsCorresponds to variant dbSNP:rs864309735EnsemblClinVar.1
    Natural variantiVAR_004410105W → R in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs121918249EnsemblClinVar.1
    Natural variantiVAR_026596108R → C in MMAM; mut0. 2 PublicationsCorresponds to variant dbSNP:rs121918257EnsemblClinVar.1
    Natural variantiVAR_026597108R → G in MMAM; mut-. 1 Publication1
    Natural variantiVAR_022394108R → H in MMAM; mut0. 3 Publications