MMUT

UniProt ID: P22033
Organism: Homo sapiens
Review Status: INITIALIZED
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Gene Description

Methylmalonyl-CoA mutase (MMUT, formerly MUT; EC 5.4.99.2) is the mitochondrial matrix adenosylcobalamin (5'-deoxyadenosylcobalamin / coenzyme B12)-dependent enzyme that catalyzes the reversible carbon-skeleton isomerization of (R)-methylmalonyl-CoA (L-methylmalonyl-CoA) to succinyl-CoA. This is the final step of propionyl-CoA catabolism, channeling propionate derived from the breakdown of the amino acids valine, isoleucine, methionine and threonine, from odd-chain fatty acids, and from the cholesterol side chain into the tricarboxylic acid cycle as succinyl-CoA. The active enzyme is a homodimer; each protomer has an N-terminal (beta/alpha)8 TIM-barrel substrate-binding domain and a C-terminal cobalamin-binding domain in which the cobalt of adenosylcobalamin is axially coordinated by a conserved histidine. Catalysis proceeds through reactive radical intermediates generated by homolysis of the cobalt-carbon bond of the cofactor. The apoenzyme is loaded with adenosylcobalamin, and inactive oxidized cofactor is removed and replaced, through a GTP-dependent interaction with the accessory GTPase MMAA (cblA), which acts together with the cobalamin adenosyltransferase MMAB (cblB). Loss of MMUT function causes isolated methylmalonic acidemia/aciduria of the mut type.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: Phylogenetic (IBA) localization to cytoplasm. MMUT is a mitochondrial-matrix enzyme; cytoplasm is a broad, less-informative localization for this protein.
Reason: MMUT is imported into the mitochondrial matrix after cleavage of its N-terminal transit peptide and its activity localizes to the mitochondria; cytoplasm captures at best a minor apoenzyme/import-intermediate pool and is far less precise than the mitochondrial-matrix annotation. The informative localization terms (mitochondrial matrix / mitochondrion) are retained.
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: COMPARTMENT OR COMPLEX MISMATCH GRANULARITY MISMATCH
Supporting Evidence:
PMID:24458
All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:1902859 propionyl-CoA catabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) assignment of MMUT to propionyl-CoA catabolism. This is the correct, non-obsolete biological-process term for MMUT's role, funneling propionate into the TCA cycle via succinyl-CoA.
Reason: MMUT catalyzes the terminal step of propionyl-CoA catabolism (methylmalonyl-CoA to succinyl-CoA); this is its core physiological pathway. Note GO:0019678 "propionate metabolic process, methylmalonyl pathway" is now obsolete, so GO:1902859 is the appropriate BP term.
Supporting Evidence:
PMID:25125334
In humans, this reaction represents an important step in propionate catabolism, funneling metabolites from the breakdown of amino acids (valine, isoleucine, methionine, and threonine), odd‐chain fatty acids, and the side chain of cholesterol into the tricarboxylic acid cycle.
GO:0004494 methylmalonyl-CoA mutase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) assignment of the defining molecular function, methylmalonyl-CoA mutase activity. This is the core function of MMUT and is strongly supported experimentally.
Reason: The IBA agrees with direct human enzyme assays and with the deeply conserved family assignment (EC 5.4.99.2). This is the central catalytic activity of the gene.
Supporting Evidence:
PMID:29056341
MUT is a mitochondrial matrix enzyme that uses coenzyme B12 or
GO:0031419 cobalamin binding
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) assignment of cobalamin binding. MMUT is an adenosylcobalamin-dependent enzyme; cobalamin (B12) binding is an essential cofactor function.
Reason: MMUT requires adenosylcobalamin (AdoCbl) as its cofactor, coordinated in the C-terminal B12-binding domain; the cobalt is axially bound by His627. Cobalamin binding is a core, experimentally supported molecular function.
Supporting Evidence:
PMID:1978672
Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme that catalyses isomerization between methylmalonyl-CoA and succinyl-CoA (3-carboxypropionyl-CoA).
GO:0005739 mitochondrion
IBA
GO_REF:0000033 		ACCEPT
Summary: Phylogenetic (IBA) mitochondrial localization. Consistent with all experimental and predictive evidence that MMUT is a mitochondrial enzyme.
Reason: MMUT carries a cleavable mitochondrial transit peptide and is active in the mitochondrial matrix; the mitochondrion annotation is correct (matrix is the more precise term, annotated separately).
Supporting Evidence:
PMID:24458
All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0003824 catalytic activity
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic assignment of the generic parent term catalytic activity. True but uninformative relative to the specific methylmalonyl-CoA mutase activity annotation.
Reason: MMUT is an enzyme, so catalytic activity is correct. It is a broad ancestor of the specific term GO:0004494; retaining it as a valid, non-misleading electronic rollup is acceptable, though it is not core.
Supporting Evidence:
PMID:25125334
catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA
GO:0004494 methylmalonyl-CoA mutase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment (multiple IEA methods, RHEA:22888 / EC 5.4.99.2) of the defining molecular function. Concordant with direct experimental evidence.
Reason: The electronic mapping to methylmalonyl-CoA mutase activity is correct and corroborated by human enzyme assays; this is the core function.
Supporting Evidence:
PMID:25125334
Mitochondrial methylmalonyl‐CoA mutase (MUT, EC 5.4.99.2) catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA, requiring vitamin B12 (cobalamin) in the form of adenosylcobalamin (AdoCbl) as a cofactor.
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		MARK AS OVER ANNOTATED
Summary: UniProt subcellular-location keyword mapping to cytoplasm (SL-0086). MMUT is a mitochondrial-matrix enzyme; cytoplasm is imprecise.
Reason: The cytoplasm keyword derives from the UniProt SUBCELLULAR LOCATION statement that lists Cytoplasm alongside Mitochondrion/matrix (from PMID:28943303), but the functional, activity-bearing localization is the mitochondrial matrix. Cytoplasm is a broad, less-informative term for MMUT.
Supporting Evidence:
PMID:24458
All of the activity of these two enzymes was demonstrated to be in the mitochondria and those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0005739 mitochondrion
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular-location keyword mapping to mitochondrion (SL-0173). Correct localization for MMUT.
Reason: MMUT is a mitochondrial protein; the electronic localization is accurate. The mitochondrial matrix annotation is the more precise term.
Supporting Evidence:
PMID:24458
All of the activity of these two enzymes was demonstrated to be in the mitochondria
GO:0005759 mitochondrial matrix
IEA
GO_REF:0000044 		ACCEPT
Summary: UniProt subcellular-location keyword mapping to mitochondrial matrix (SL-0170). This is the precise, correct localization of the active enzyme.
Reason: Direct fractionation studies localize MMUT activity to the mitochondrial matrix (loosely bound to the inner membrane-matrix compartment); the electronic annotation matches the experimental evidence.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0016853 isomerase activity
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic assignment of the parent term isomerase activity. True (MMUT is an intramolecular isomerase/mutase) but broad relative to GO:0004494.
Reason: MMUT is EC 5.4.99.2, an isomerase; the term is a correct ancestor of the specific methylmalonyl-CoA mutase activity term. Valid non-core electronic rollup.
Supporting Evidence:
PMID:25125334
catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA
GO:0016866 intramolecular transferase activity
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic assignment of intramolecular transferase activity (mutase). Correct intermediate parent of methylmalonyl-CoA mutase activity.
Reason: Methylmalonyl-CoA mutase is a carbon-skeleton mutase (intramolecular transfer of the thioester/carboxyl-bearing group), so GO:0016866 is an accurate ancestor of the specific term. Valid non-core electronic rollup.
Supporting Evidence:
PMID:25125334
catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA
GO:0031419 cobalamin binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic assignment of cobalamin binding, based on the B12-binding domain signatures. Concordant with the experimental cofactor requirement.
Reason: MMUT contains a cobalamin-binding domain and requires adenosylcobalamin; the electronic annotation matches the direct experimental evidence for cofactor binding.
Supporting Evidence:
PMID:1978672
Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme
GO:0046872 metal ion binding
IEA
GO_REF:0000002 		ACCEPT
Summary: InterPro2GO electronic assignment of metal ion binding, reflecting the cobalt ion of the bound adenosylcobalamin cofactor.
Reason: The cofactor adenosylcobalamin contains a cobalt ion that is axially coordinated by His627 of MMUT, so metal (cobalt) ion binding is correct, if broad. It is captured more informatively by cobalamin binding.
Supporting Evidence:
PMID:20876572
vitamin B12-dependent methylmalonyl-CoA mutase
GO:0005515 protein binding
IPI
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		MARK AS OVER ANNOTATED
Summary: IntAct IPI (partner MMAA, Q8IVH4). Bare protein binding is uninformative as a molecular function; the biologically meaningful apo-MUT:MMAA interaction is captured by the homodimerization and positive-regulation-of-GTPase annotations.
Reason: Per curation guidance, generic protein binding does not convey a specific molecular function and should not be treated as a core annotation. The underlying MMAA interaction is real and is documented; it is represented more usefully elsewhere.
Supporting Evidence:
PMID:20876572
the two proteins interact in vitro and in vivo
GO:0005515 protein binding
IPI
PMID:28497574
Protein destabilization and loss of protein-protein interact... 		MARK AS OVER ANNOTATED
Summary: IntAct IPI (partner MMAA, Q8IVH4) from the cblA-type MMA study. Bare protein binding is uninformative.
Reason: Generic protein binding is not an informative molecular function. The MUT-MMAA interaction it reflects is documented, but is better represented by the positive-regulation-of-GTPase-activity annotation.
Supporting Evidence:
PMID:28497574
which is stimulated by an interaction with MUT
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		MARK AS OVER ANNOTATED
Summary: IntAct IPI (partner HTT/huntingtin, P42858) from a neurodegenerative-disease interactome map. Bare protein binding is uninformative and this is a large-scale network interaction of uncertain physiological relevance to MMUT function.
Reason: Generic protein binding conveys no specific molecular function. This is a high-throughput interactome/aggregation screen; the interaction does not inform MMUT's characterized enzymatic role.
Supporting Evidence:
PMID:32814053
Interactome maps are valuable resources to elucidate protein function and disease mechanisms.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling... 		MARK AS OVER ANNOTATED
Summary: IntAct IPI (partner CRYZ, Q08257) from a proteome-scale interactome study. Bare protein binding is uninformative.
Reason: Generic protein binding is not an informative molecular function. This is a large-scale affinity-purification network dataset; the interaction does not inform MMUT's core function.
Supporting Evidence:
PMID:33961781
These networks model the interactome
GO:0005515 protein binding
IPI
PMID:40205054
Multimodal cell maps as a foundation for structural and func... 		MARK AS OVER ANNOTATED
Summary: IntAct IPI (partner CRYZ, Q08257) from a multimodal cell-map study. Bare protein binding is uninformative.
Reason: Generic protein binding conveys no specific molecular function. This is a large-scale mapping dataset; the interaction does not inform MMUT's core function.
Supporting Evidence:
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
GO:0042802 identical protein binding
IPI
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		KEEP AS NON CORE
Summary: IntAct IPI (self, P22033), reflecting the MMUT homodimer. Real but represented more informatively by protein homodimerization activity.
Reason: MMUT is a homodimer, so self-association is genuine, but identical protein binding is a weaker restatement of the homodimerization annotation; keep as non-core.
Supporting Evidence:
PMID:20876572
crystallized human MMAA in the GDP-bound form and human MUT in the apo, holo, and substrate-bound ternary forms
GO:1901290 succinyl-CoA biosynthetic process
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic assignment of succinyl-CoA biosynthetic process. This is an accurate product-oriented description of the MMUT reaction (MM-CoA to succinyl-CoA).
Reason: MMUT produces succinyl-CoA from methylmalonyl-CoA; the term correctly describes the product-forming aspect of its reaction. Complementary to the propionyl-CoA catabolic process annotation.
Supporting Evidence:
PMID:29056341
It catalyzes the conversion of methylmalonyl-CoA into succinyl-CoA, which allows recycling of branched carbon chains from amino acids and lipids into the tricarboxylic acid cycle (TCA cycle).
GO:0004494 methylmalonyl-CoA mutase activity
EXP
PMID:1346616
Cloning and expression of a mutant methylmalonyl coenzyme A ... 		ACCEPT
Summary: Experimental (EXP) demonstration of methylmalonyl-CoA mutase activity via cloning and expression of human MCM and characterization of a cobalamin-affinity mutant. Core function.
Reason: This study expressed human MCM and characterized its catalytic behavior (including the G717V mut- mutant with ~1000-fold elevated Km for adenosylcobalamin), directly supporting methylmalonyl-CoA mutase activity as the gene's function.
Supporting Evidence:
PMID:1346616
an apparent Km (adenosylcobalamin) 1,000-fold higher than normal
GO:0004494 methylmalonyl-CoA mutase activity
EXP
PMID:25125334
Functional characterization and categorization of missense m... 		ACCEPT
Summary: Experimental (EXP) characterization of MUT activity across 23 recombinant patient missense variants, measuring succinate production from methylmalonyl-CoA. Core function.
Reason: Wild-type and mutant MUT were assayed for conversion of [14C]methylmalonyl-CoA to [14C]succinate, directly measuring methylmalonyl-CoA mutase activity and its cofactor/substrate kinetics.
Supporting Evidence:
PMID:25125334
MUT activity was assayed in crude cell lysates by measuring the production of [14C]succinate from [14C]methylmalonyl‐CoA
GO:0004494 methylmalonyl-CoA mutase activity
EXP
PMID:29056341
The Human Knockout Gene CLYBL Connects Itaconate to Vitamin ... 		ACCEPT
Summary: Experimental (EXP) work using recombinant human MUT reconstituted with coenzyme B12; establishes methylmalonyl-CoA mutase activity and its inhibition by itaconyl-CoA. Core function.
Reason: The study characterized recombinant human MUT enzymology (conversion of methylmalonyl-CoA to succinyl-CoA using coenzyme B12) and identified itaconyl-CoA as a cofactor-inactivating inhibitor, directly supporting the mutase activity.
Supporting Evidence:
PMID:29056341
itaconyl-CoA is a cofactor-inactivating, substrate-analog inhibitor of the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT)
GO:1901290 succinyl-CoA biosynthetic process
IDA
PMID:1978672
Primary structure and activity of mouse methylmalonyl-CoA mu... 		ACCEPT
Summary: Direct assay (IDA) of mutase activity producing succinyl-CoA from methylmalonyl-CoA. Accurate product-oriented description of the MMUT reaction.
Reason: Enzyme assays of MCM demonstrated isomerization between methylmalonyl-CoA and succinyl-CoA, supporting involvement in succinyl-CoA biosynthesis.
Supporting Evidence:
PMID:1978672
an adenosylcobalamin-dependent enzyme that catalyses isomerization between methylmalonyl-CoA and succinyl-CoA (3-carboxypropionyl-CoA)
GO:0005739 mitochondrion
HTP
PMID:34800366
Quantitative high-confidence human mitochondrial proteome an... 		ACCEPT
Summary: High-throughput (HTP) mitochondrial proteome study placing MMUT among the high-confidence mitochondrial proteins (MitoCoP). Consistent with all other evidence.
Reason: MMUT was classified in the >1,100-protein high-confidence human mitochondrial proteome, corroborating its mitochondrial localization.
Supporting Evidence:
PMID:34800366
defined a mitochondrial high-confidence proteome of >1,100 proteins (MitoCoP)
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-3322971 		ACCEPT
Summary: Reactome traceable assertion (TAS) placing MMUT in the mitochondrial matrix (in the context of defective MUT failing to isomerise L-MM-CoA to succinyl-CoA). Correct localization.
Reason: Reactome curates MMUT as a mitochondrial matrix enzyme; consistent with direct fractionation evidence.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0004494 methylmalonyl-CoA mutase activity
IDA
PMID:1978672
Primary structure and activity of mouse methylmalonyl-CoA mu... 		ACCEPT
Summary: Direct assay (IDA) of methylmalonyl-CoA mutase activity for the cloned enzyme, with reaction kinetics similar to the human enzyme. Core function.
Reason: The enzyme was directly assayed and shown to isomerize methylmalonyl-CoA to succinyl-CoA in an adenosylcobalamin-dependent manner, defining the core molecular function.
Supporting Evidence:
PMID:1978672
catalyses isomerization between methylmalonyl-CoA and succinyl-CoA (3-carboxypropionyl-CoA)
GO:0004494 methylmalonyl-CoA mutase activity
IDA
PMID:21138732
Protection and reactivation of human methylmalonyl-CoA mutas... 		ACCEPT
Summary: Direct assay (IDA) of purified recombinant human MCM catalytic activity (and its protection/reactivation by MMAA). Core function.
Reason: Purified recombinant MCM was assayed for its methylmalonyl-CoA mutase reaction kinetics, directly establishing the activity.
Supporting Evidence:
PMID:21138732
we examined the influence of human MMAA protein on the kinetics of the reaction catalyzed by methylmalonyl-CoA mutase (MCM) by testing both purified recombinant proteins in vitro
GO:0004494 methylmalonyl-CoA mutase activity
IDA
PMID:24458
Intracellular localization of hepatic propionyl-CoA carboxyl... 		ACCEPT
Summary: Direct assay (IDA) of methylmalonyl-CoA mutase activity in hepatic mitochondrial fractions (a rapid mutase assay was described). Core function.
Reason: Methylmalonyl-CoA mutase activity was measured in mitochondrial fractions of human and rat liver, directly supporting the molecular function and its mitochondrial localization.
Supporting Evidence:
PMID:24458
a rapid enzymatic assay for methylmalonyl-CoA mutase was described.
GO:0004494 methylmalonyl-CoA mutase activity
IDA
PMID:2453061
Molecular cloning of L-methylmalonyl-CoA mutase: gene transf... 		ACCEPT
Summary: Direct assay (IDA) of MCM activity constituted by gene transfer of the cloned human MCM cDNA into COS cells. Core function.
Reason: Cells transformed with the human MCM cDNA expressed increased methylmalonyl-CoA mutase enzymatic activity, directly demonstrating the function of the cloned gene.
Supporting Evidence:
PMID:2453061
Cells transformed with this clone expressed increased levels of MCM enzymatic activity.
GO:0004494 methylmalonyl-CoA mutase activity
IDA
PMID:28943303
Human MMAA induces the release of inactive cofactor and rest... 		ACCEPT
Summary: Direct assay (IDA) of recombinant human MCM activity, including altered kinetics in the presence of MMAA/GTP. Core function.
Reason: Recombinant hMCM was assayed for its mutase reaction and cofactor kinetics (Km/Vmax for methylmalonyl-CoA), directly establishing methylmalonyl-CoA mutase activity.
Supporting Evidence:
PMID:28943303
Human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase that converts methylmalonyl-CoA to succinyl-CoA
GO:0005515 protein binding
IPI
PMID:21138732
Protection and reactivation of human methylmalonyl-CoA mutas... 		MARK AS OVER ANNOTATED
Summary: IPI (partner MMAA, Q8IVH4). MUT-MMAA interaction confirmed by yeast two-hybrid. Bare protein binding is uninformative as an MF.
Reason: Generic protein binding is not an informative molecular function. The real MUT-MMAA interaction is documented and is better represented by the positive-regulation-of-GTPase-activity annotation.
Supporting Evidence:
PMID:21138732
Interaction between MCM and MMAA observed in vitro was confirmed in vivo by yeast two-hybrid system.
GO:0005515 protein binding
IPI
PMID:28943303
Human MMAA induces the release of inactive cofactor and rest... 		MARK AS OVER ANNOTATED
Summary: IPI (partner MMAA, Q8IVH4). Bare protein binding is uninformative as an MF; the MUT-MMAA complex is the biologically meaningful interaction.
Reason: Generic protein binding conveys no specific molecular function. The MUT-MMAA complex formation demonstrated here is better captured by the regulatory and localization annotations.
Supporting Evidence:
PMID:28943303
restores methylmalonyl-CoA mutase activity through their complex formation
GO:0005737 cytoplasm
IDA
PMID:28943303
Human MMAA induces the release of inactive cofactor and rest... 		MARK AS OVER ANNOTATED
Summary: Direct-assay (IDA) localization including a cytoplasmic signal in human fibroblasts. MMUT is a mitochondrial-matrix enzyme; cytoplasm is imprecise/over-broad.
Reason: This study reported the in vivo localization and colocalization of hMMAA with hMCM in fibroblast mitochondria; the functional pool of MMUT is mitochondrial-matrix. Cytoplasm at best reflects a minor apoenzyme/import-intermediate signal and is a less informative localization than the mitochondrial matrix annotation.
Supporting Evidence:
PMID:28943303
the in vivo localization of hMMAA and its colocalization with hMCM in human fibroblasts mitochondria were demonstrated.
GO:0005739 mitochondrion
IDA
PMID:28943303
Human MMAA induces the release of inactive cofactor and rest... 		ACCEPT
Summary: Direct-assay (IDA) mitochondrial localization of hMCM in human fibroblasts. Correct localization.
Reason: Immunolocalization showed hMCM in fibroblast mitochondria (colocalizing with hMMAA), directly supporting the mitochondrial annotation.
Supporting Evidence:
PMID:28943303
the in vivo localization of hMMAA and its colocalization with hMCM in human fibroblasts mitochondria were demonstrated.
GO:0005759 mitochondrial matrix
IDA
PMID:24458
Intracellular localization of hepatic propionyl-CoA carboxyl... 		ACCEPT
Summary: Direct-assay (IDA) localization of MMUT activity to the mitochondrial inner-membrane/matrix compartment by subcellular fractionation. Precise, core localization.
Reason: All MMUT activity fractionated with mitochondria and was loosely bound to the inner membrane-matrix portion, directly establishing the mitochondrial-matrix localization.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0031419 cobalamin binding
IDA
PMID:1978672
Primary structure and activity of mouse methylmalonyl-CoA mu... 		ACCEPT
Summary: Direct assay (IDA) establishing adenosylcobalamin dependence/binding (cofactor requirement, Km for adenosylcobalamin). Core cofactor function.
Reason: The enzyme is adenosylcobalamin-dependent with a defined Km for the cofactor, directly supporting cobalamin binding.
Supporting Evidence:
PMID:1978672
Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme
GO:0031419 cobalamin binding
IDA
PMID:21138732
Protection and reactivation of human methylmalonyl-CoA mutas... 		ACCEPT
Summary: Direct assay (IDA) of the cobalamin cofactor role, including cofactor oxidation during catalysis and its exchange by MMAA. Core cofactor function.
Reason: The study addressed inactivation due to oxidation of the bound cobalamin and its reactivation by cofactor exchange, directly supporting cobalamin binding by MCM.
Supporting Evidence:
PMID:21138732
some adenosylcobalamin-dependent enzymes suffer inactivation during catalysis due to the oxidation of cobalamin
GO:0031419 cobalamin binding
IDA
PMID:28943303
Human MMAA induces the release of inactive cofactor and rest... 		ACCEPT
Summary: Direct assay (IDA) of the AdoCbl cofactor role, including OH2Cbl formation and removal/replacement of damaged cofactor. Core cofactor function.
Reason: hMCM uses adenosylcobalamin (AdoCbl) and its oxidized inactive form (OH2Cbl) is removed via MMAA, directly supporting cobalamin binding.
Supporting Evidence:
PMID:28943303
employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl)
GO:0003924 GTPase activity
IDA
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		UNDECIDED
Summary: IDA annotation of GTPase activity to MMUT. In this paper the demonstrated GTPase is MMAA (the partner protein), whose GTPase activity is modulated by MUT; MUT itself is a B12 mutase with no GTPase domain.
Reason: The abstract explicitly attributes GTPase activity to MMAA ("MMAA exhibits GTPase activity that is modulated by MUT"), and MMUT has no P-loop/GTPase fold, so assigning GTPase activity to MMUT appears to be a mis-attribution of the partner's activity. However, per curation policy I cannot read the full text to confirm exactly what was assayed for MMUT, so I flag this rather than removing an experimental annotation; if the assignment cannot be substantiated it should be removed.
Supporting Evidence:
PMID:20876572
MMAA exhibits GTPase activity that is modulated by MUT
GO:0031419 cobalamin binding
IDA
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		ACCEPT
Summary: Direct assay/structure (IDA) with adenosylcobalamin bound to MUT (holo and ternary crystal structures), supporting cobalamin binding. Core cofactor function.
Reason: The crystal structures of human MUT were solved in apo, holo, and substrate-bound (ternary) forms with adenosylcobalamin, directly demonstrating cobalamin binding (the cobalt is axially coordinated by His627).
Supporting Evidence:
PMID:20876572
human MUT in the apo, holo, and substrate-bound ternary forms
GO:0042802 identical protein binding
IDA
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		KEEP AS NON CORE
Summary: IDA of self-association (MMUT homodimer) from crystallographic subunit analysis. Real but a weaker restatement of homodimerization activity.
Reason: MMUT is a homodimer, so identical protein binding is genuine; it duplicates the more informative protein homodimerization activity annotation and is not a core function.
Supporting Evidence:
PMID:20876572
they show substantially different dimeric assembly and interaction
GO:0042803 protein homodimerization activity
IDA
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		KEEP AS NON CORE
Summary: IDA of homodimerization from the human MUT crystal structure. MMUT is an active homodimer; a genuine, structurally supported property.
Reason: The human MUT crystal structures establish a homodimeric assembly. This is a real structural property enabling function, but it is ancillary to the core catalytic annotation.
Supporting Evidence:
PMID:20876572
they show substantially different dimeric assembly and interaction, compared with their bacterial counterparts
GO:0043547 positive regulation of GTPase activity
IDA
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependen... 		KEEP AS NON CORE
Summary: IDA that MUT modulates (stimulates) the GTPase activity of its partner MMAA. A genuine regulatory role, but ancillary to MMUT's core catalytic function.
Reason: The apo-MUT:MMAA interaction modulates MMAA's GTPase activity; this GAP-like regulatory role is documented but is peripheral to MMUT's core mutase function.
Supporting Evidence:
PMID:20876572
MMAA exhibits GTPase activity that is modulated by MUT
GO:0043547 positive regulation of GTPase activity
IDA
PMID:28497574
Protein destabilization and loss of protein-protein interact... 		KEEP AS NON CORE
Summary: IDA that MUT stimulates MMAA GTPase activity; loss of this stimulation underlies cblA-type MMA. Genuine regulatory role, ancillary to core function.
Reason: MMAA's GTPase activity is stimulated by interaction with MUT, and disease mutations reduce this stimulation; the regulatory role is supported but is not MMUT's core function.
Supporting Evidence:
PMID:28497574
This function of MMAA depends on its GTPase activity, which is stimulated by an interaction with MUT.
GO:0004494 methylmalonyl-CoA mutase activity
IMP
PMID:28101778
Eight novel MUT loss-of-function missense mutations in Chine... 		ACCEPT
Summary: IMP evidence from patient loss-of-function missense mutations that reduce MCM enzymatic activity in a functional assay. Supports the core mutase function.
Reason: Eight novel MUT missense mutations reduced MCM protein and activity in a permissive assay, genetically implicating MMUT in methylmalonyl-CoA mutase activity.
Supporting Evidence:
PMID:28101778
the MCM activity of the mutations was reduced in a permissive assay.
GO:0004494 methylmalonyl-CoA mutase activity
IMP
PMID:27167370
Molecular Genetic Characterization of 151 Mut-Type Methylmal... 		ACCEPT
Summary: IMP evidence from a large mut-type MMA patient cohort (110 mutations) showing reduced MUT protein/activity. Supports the core mutase function.
Reason: Molecular-genetic characterization of 151 mut-type MMA patients links MUT mutations to loss of MUT function (reduced protein and propionate incorporation), supporting methylmalonyl-CoA mutase activity as the gene's function.
Supporting Evidence:
PMID:27167370
Western blot analysis revealed reduced MUT protein for all 34 cell lines (27 mut(0) , seven mut(-) ) tested, suggesting protein instability as a major mechanism of deficiency in mut-type MMA.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-3159259 		ACCEPT
Summary: Reactome TAS placing MMUT in the mitochondrial matrix (MMAA:MUT binds AdoCbl reaction). Correct localization.
Reason: Reactome curates MMUT (and the MMAA:MUT complex) in the mitochondrial matrix, consistent with the experimental localization.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-3322135 		ACCEPT
Summary: Reactome TAS placing MMUT in the mitochondrial matrix (Defective MMAA does not protect MUT reaction). Correct localization.
Reason: Reactome consistently curates MMUT in the mitochondrial matrix; consistent with the experimental fractionation evidence.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0005759 mitochondrial matrix
TAS
Reactome:R-HSA-71010 		ACCEPT
Summary: Reactome TAS placing MMUT in the mitochondrial matrix (MUT isomerises L-MM-CoA to SUCC-CoA reaction). Correct localization for the catalytic step.
Reason: Reactome curates the MUT-catalyzed isomerization of L-methylmalonyl-CoA to succinyl-CoA in the mitochondrial matrix, matching the experimental localization.
Supporting Evidence:
PMID:24458
those enzymes were shown to be loosely bound to the inner membrane-matrix portion of the mitochondria.
GO:0050667 homocysteine metabolic process
IDA
PMID:20031578
Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma... 		MARK AS OVER ANNOTATED
Summary: Annotation derived from a GWAS association of a MUT-locus SNP with plasma homocysteine. The paper itself states MUT's catalytic activity is "hardly related to homocysteine"; any link is indirect (shared B12 dependence), not a direct molecular role of MMUT in homocysteine metabolism.
Reason: The association is epidemiological/genetic and, per the authors, only indirectly related to MMUT function (via competition for vitamin B12 between mitochondrial MUT and cytosolic methionine synthase). MMUT does not act on homocysteine or its metabolites, so involvement in homocysteine metabolic process is an over-annotation.
Supporting Evidence:
PMID:20031578
While its catalytic activity is hardly related to homocysteine, MUT has frequently been associated with homocysteine metabolism because it is one of three vitamin B 12 dependant enzymes
GO:0072341 modified amino acid binding
IDA
PMID:20031578
Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma... 		MARK AS OVER ANNOTATED
Summary: Annotation from the same homocysteine GWAS paper. There is no biochemical demonstration that MMUT binds a modified amino acid; its characterized ligands are methylmalonyl-CoA and adenosylcobalamin.
Reason: The GWAS study did not assay MMUT binding to any modified amino acid; MMUT's substrate is a CoA thioester and its cofactor is a corrinoid, not a modified amino acid. This molecular-function annotation does not fit the characterized biochemistry.
Supporting Evidence:
PMID:20031578
MUT encodes for the mitochondrial enzyme methylmalonyl-Coa mutase and as such, catalyses the isomeration of methylmalonyl-Coa into succinyl-Coa.
GO:0005739 mitochondrion
TAS
PMID:2567699
Cloning of full-length methylmalonyl-CoA mutase from a cDNA ... 		ACCEPT
Summary: Traceable assertion (TAS) of mitochondrial localization; the full-length cDNA cloning identified the N-terminal mitochondrial transit peptide. Correct localization.
Reason: The cloning of full-length human MCM defined its mitochondrial-targeting N-terminus (the transit peptide, residues 1-32), supporting mitochondrial localization.
Supporting Evidence:
PMID:2567699
Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.

Core Functions

Adenosylcobalamin (coenzyme B12)-dependent methylmalonyl-CoA mutase that catalyzes the reversible isomerization of (R)-methylmalonyl-CoA (L-methylmalonyl-CoA) to succinyl-CoA, the terminal step of propionyl-CoA catabolism, in the mitochondrial matrix.

Molecular Function:
methylmalonyl-CoA mutase activity
Directly Involved In:
propionyl-CoA catabolic process
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • PMID:25125334
    Mitochondrial methylmalonyl‐CoA mutase (MUT, EC 5.4.99.2) catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA, requiring vitamin B12 (cobalamin) in the form of adenosylcobalamin (AdoCbl) as a cofactor. In humans, this reaction represents an important step in propionate catabolism

Binds adenosylcobalamin (vitamin B12) as an essential catalytic cofactor; the cobalt of the corrinoid is axially coordinated by a conserved histidine in the C-terminal cobalamin-binding domain, and homolysis of the cobalt-carbon bond generates the radical intermediates required for isomerization.

Molecular Function:
cobalamin binding
Cellular Locations:
mitochondrial matrix
Supporting Evidence:
  • PMID:1978672
    Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme that catalyses isomerization between methylmalonyl-CoA and succinyl-CoA
  • PMID:28943303
    employs highly reactive radicals from its cofactor (adenosylcobalamin, AdoCbl)

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:1346616
Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin affinity that causes mut- methylmalonic aciduria.
PMID:1978672
Primary structure and activity of mouse methylmalonyl-CoA mutase.
PMID:20031578
Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study.
PMID:20876572
Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.
PMID:21138732
Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein.
PMID:24458
Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA mutase in humans and normal and vitamin B12 deficient rats.
PMID:2453061
Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut cell lines.
PMID:25125334
Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA mutase (MUT) deficiency.
PMID:2567699
Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase chain reaction.
PMID:27167370
Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT.
PMID:28101778
Eight novel MUT loss-of-function missense mutations in Chinese patients with isolated methylmalonic academia.
PMID:28497574
Protein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria.
PMID:28943303
Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA mutase activity through their complex formation.
PMID:29056341
The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B(12).
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
PMID:34800366
Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.
PMID:40205054
Multimodal cell maps as a foundation for structural and functional genomics.
Reactome:R-HSA-3159259
MMAA:MUT binds AdoCbl
Reactome:R-HSA-3322135
Defective MMAA does not protect MUT
Reactome:R-HSA-3322971
Defective MUT does not isomerise L-MM-CoA to SUCC-CoA
Reactome:R-HSA-71010
MUT isomerises L-MM-CoA to SUCC-CoA

📚 Additional Documentation

Notes

(MMUT-notes.md)

MMUT (P22033) review notes

Deep research file MMUT-deep-research-falcon.md did not materialize within the 8-min poll
window; review grounded in the UniProt record (MMUT-uniprot.txt), seeded GOA
(MMUT-goa.tsv), cached publications/PMID_*.md, and the disorder KB
~/repos/dismech/kb/disorders/Methylmalonic_Acidemia.yaml.

Core biology (well established)

  • MMUT (formerly MUT; UniProt MUTA_HUMAN, EC 5.4.99.2) is the mitochondrial-matrix
    adenosylcobalamin (AdoCbl / coenzyme B12)-dependent methylmalonyl-CoA mutase. It
    catalyses the reversible carbon-skeleton isomerization (R)-methylmalonyl-CoA
    (L-methylmalonyl-CoA) <-> succinyl-CoA     (Rhea:RHEA:22888), the final step of
    propionyl-CoA catabolism [PMID:25125334, PMID:29056341, UniProt CC FUNCTION].
  • Physiological direction is left-to-right (MM-CoA -> succinyl-CoA); this funnels
    propionate derived from Ile/Val/Met/Thr, odd-chain fatty acids, and the cholesterol
    side chain into the TCA cycle as succinyl-CoA (anaplerosis) [PMID:25125334, PMID:29056341].
  • Homodimer (PDB 2XIJ/2XIQ/3BIC); each protomer has an N-terminal (β/α)8 TIM-barrel
    substrate-binding domain and a C-terminal B12-binding domain (residues ~614-746). The
    cofactor Co is axially coordinated by His627 [UniProt FT BINDING 627; PMID:20876572].
  • Cofactor delivery / repair: apo-MUT interacts with the MMAA GTPase (cblA) in a
    GTP-dependent manner; MMAA gates loading of AdoCbl (made by MMAB, cblB) into MUT
    and, via GTP hydrolysis, removes/replaces oxidized inactive cofactor (OH2Cbl) formed
    during catalysis, protecting/reactivating MUT [PMID:20876572, PMID:21138732, PMID:28943303].
  • Inhibited by itaconyl-CoA, a suicide substrate analog that inactivates the B12 cofactor
    (links immunometabolite itaconate / CLYBL loss to functional B12 deficiency)
    PMID:29056341; also inhibited by malyl-CoA [UniProt CC, PMID:40108300].
  • Disease: biallelic loss-of-function -> isolated methylmalonic aciduria/acidemia,
    mut type (MAMM; MIM 251000)    , mut0 (no residual activity) vs mut- (residual, partly
    OHCbl-responsive). Distinct from cblA (MMAA) and cblB (MMAB) cofactor-delivery defects
    [PMID:25125334, PMID:27167370, PMID:28101778; disorder KB].

Annotation triage rationale

  • GO:0004494 methylmalonyl-CoA mutase activity — core MF. Supported by many EXP/IDA/IMP
    and IBA/IEA lines. ACCEPT all (duplicates across evidence codes are fine).
  • GO:0031419 cobalamin binding — core MF (AdoCbl cofactor). ACCEPT (IDA + IBA); IEA ACCEPT.
  • GO:1902859 propionyl-CoA catabolic process (IBA) — correct BP; the valid,
    non-obsolete term for MUT's pathway role (GO:0019678 "propionate metabolic process,
    methylmalonyl pathway" is now OBSOLETE). ACCEPT; use as core BP.
  • GO:1901290 succinyl-CoA biosynthetic process (IDA PMID:1978672; IEA) — accurate
    product-oriented description of the same reaction. ACCEPT (IDA); IEA ACCEPT.
  • GO:0005759 mitochondrial matrix (IDA PMID:24458; TAS Reactome; IEA) — correct
    localization. ACCEPT the experimental/loosest one as core; keep others.
  • GO:0005739 mitochondrion (IBA/IEA/IDA/HTP/TAS) — parent of matrix; ACCEPT.
  • GO:0005737 cytoplasm (IBA/IEA/IDA PMID:28943303) — MUT is matrix; cytoplasm is a
    broad/less-precise localization (UniProt lists Cytoplasm from PMID:28943303, likely
    reflecting apoenzyme/import-intermediate pool). MARK_AS_OVER_ANNOTATED (imprecise; matrix
    is the informative term). Not REMOVE (has an IDA behind it).
  • GO:0003824 catalytic activity / GO:0016853 isomerase activity / GO:0016866
    intramolecular transferase activity     (IEA InterPro) — correct but general ancestors of
    GO:0004494. Keep (ACCEPT the broad ones as non-misleading IEA rollups; they are valid,
    just less specific). Per guidance, broad IEAs above a well-supported specific term can be
    accepted.
  • GO:0046872 metal ion binding (IEA) — MUT binds Co (in AdoCbl). Broad but true. ACCEPT.
  • GO:0005515 protein binding (IPI x7, various partners: MMAA Q8IVH4, HTT P42858,
    CRYZ Q08257) — bare, uninformative MF. Per policy MARK_AS_OVER_ANNOTATED (do not REMOVE
    IPIs; do not attach a functional MF label). The biologically meaningful interaction
    (apo-MUT with MMAA) is captured better elsewhere.
  • GO:0042802 identical protein binding / GO:0042803 protein homodimerization activity
    (IDA PMID:20876572) — MUT is a homodimer; homodimerization is real and structurally
    supported. ACCEPT homodimerization (informative); identical protein binding is the
    weaker synonym — KEEP_AS_NON_CORE.
  • GO:0003924 GTPase activity (IDA PMID:20876572) — the GTPase in that paper is MMAA,
    not MUT. MUT has no GTPase activity/domain (no P-loop; it is a B12 mutase). This IDA
    appears to be a mis-assignment of MMAA's activity to its partner MUT. However, per the
    do-not-overrule-experimental-IDA policy and inability to read full text to confirm the
    assay attribution, use UNDECIDED (flag the concern; the abstract explicitly attributes
    GTPase activity to MMAA and shows it is "modulated by MUT").
  • GO:0043547 positive regulation of GTPase activity (IDA PMID:20876572, PMID:28497574)
    — MUT (apoenzyme) stimulates MMAA's GTPase activity via their interaction; this is
    documented (28497574: GTPase activity "stimulated by an interaction with MUT"). ACCEPT
    as KEEP_AS_NON_CORE (regulatory, not the core catalytic function).
  • GO:0050667 homocysteine metabolic process (IDA PMID:20031578) — this is a GWAS
    association of a MUT-locus SNP with plasma homocysteine; the paper itself states MUT's
    "catalytic activity is hardly related to homocysteine." Not a direct molecular role of
    MUT in homocysteine metabolism. MARK_AS_OVER_ANNOTATED (indirect/associative; not a
    bona fide involvement). Not REMOVE per policy caution around experimental codes, but the
    claim is only an epidemiological/mechanistically-indirect link.
  • GO:0072341 modified amino acid binding (IDA PMID:20031578) — same GWAS paper; there
    is no biochemical demonstration that MUT binds a modified amino acid. The term does not
    fit MUT's characterized ligands (methylmalonyl-CoA, AdoCbl). MARK_AS_OVER_ANNOTATED.

core_functions (author-supplied ids — strictly validated against current go.db)

  • MF: GO:0004494 methylmalonyl-CoA mutase activity
  • MF (cofactor): GO:0031419 cobalamin binding
  • directly_involved_in BP: GO:1902859 propionyl-CoA catabolic process
  • location: GO:0005759 mitochondrial matrix

📄 View Raw YAML

 
id: P22033
gene_symbol: MMUT
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: Methylmalonyl-CoA mutase (MMUT, formerly MUT; EC 5.4.99.2) is the mitochondrial
  matrix adenosylcobalamin (5'-deoxyadenosylcobalamin / coenzyme B12)-dependent enzyme
  that catalyzes the reversible carbon-skeleton isomerization of (R)-methylmalonyl-CoA
  (L-methylmalonyl-CoA) to succinyl-CoA. This is the final step of propionyl-CoA catabolism,
  channeling propionate derived from the breakdown of the amino acids valine, isoleucine,
  methionine and threonine, from odd-chain fatty acids, and from the cholesterol side chain
  into the tricarboxylic acid cycle as succinyl-CoA. The active enzyme is a homodimer;
  each protomer has an N-terminal (beta/alpha)8 TIM-barrel substrate-binding domain and a
  C-terminal cobalamin-binding domain in which the cobalt of adenosylcobalamin is axially
  coordinated by a conserved histidine. Catalysis proceeds through reactive radical
  intermediates generated by homolysis of the cobalt-carbon bond of the cofactor. The
  apoenzyme is loaded with adenosylcobalamin, and inactive oxidized cofactor is removed
  and replaced, through a GTP-dependent interaction with the accessory GTPase MMAA (cblA),
  which acts together with the cobalamin adenosyltransferase MMAB (cblB). Loss of MMUT
  function causes isolated methylmalonic acidemia/aciduria of the mut type.
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) localization to cytoplasm. MMUT is a mitochondrial-matrix
      enzyme; cytoplasm is a broad, less-informative localization for this protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: MMUT is imported into the mitochondrial matrix after cleavage of its N-terminal
      transit peptide and its activity localizes to the mitochondria; cytoplasm captures at
      best a minor apoenzyme/import-intermediate pool and is far less precise than the
      mitochondrial-matrix annotation. The informative localization terms (mitochondrial
      matrix / mitochondrion) are retained.
    propagation_review:
      root_cause: TERM_SCOPING_PROBLEM
      failure_modes:
      - COMPARTMENT_OR_COMPLEX_MISMATCH
      - GRANULARITY_MISMATCH
    supported_by:
    - reference_id: PMID:24458
      supporting_text: All of the activity of these two enzymes was demonstrated to be in
        the mitochondria and those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:1902859
    label: propionyl-CoA catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) assignment of MMUT to propionyl-CoA catabolism. This is the
      correct, non-obsolete biological-process term for MMUT's role, funneling propionate
      into the TCA cycle via succinyl-CoA.
    action: ACCEPT
    reason: MMUT catalyzes the terminal step of propionyl-CoA catabolism (methylmalonyl-CoA
      to succinyl-CoA); this is its core physiological pathway. Note GO:0019678 "propionate
      metabolic process, methylmalonyl pathway" is now obsolete, so GO:1902859 is the
      appropriate BP term.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: In humans, this reaction represents an important step in propionate
        catabolism, funneling metabolites from the breakdown of amino acids (valine,
        isoleucine, methionine, and threonine), odd‐chain fatty acids, and the side chain
        of cholesterol into the tricarboxylic acid cycle.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of the defining molecular function,
      methylmalonyl-CoA mutase activity. This is the core function of MMUT and is strongly
      supported experimentally.
    action: ACCEPT
    reason: The IBA agrees with direct human enzyme assays and with the deeply conserved
      family assignment (EC 5.4.99.2). This is the central catalytic activity of the gene.
    supported_by:
    - reference_id: PMID:29056341
      supporting_text: MUT is a mitochondrial matrix enzyme that uses coenzyme B12 or
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic (IBA) assignment of cobalamin binding. MMUT is an
      adenosylcobalamin-dependent enzyme; cobalamin (B12) binding is an essential cofactor
      function.
    action: ACCEPT
    reason: MMUT requires adenosylcobalamin (AdoCbl) as its cofactor, coordinated in the
      C-terminal B12-binding domain; the cobalt is axially bound by His627. Cobalamin
      binding is a core, experimentally supported molecular function.
    supported_by:
    - reference_id: PMID:1978672
      supporting_text: Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent
        enzyme that catalyses isomerization between methylmalonyl-CoA and succinyl-CoA
        (3-carboxypropionyl-CoA).
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Phylogenetic (IBA) mitochondrial localization. Consistent with all
      experimental and predictive evidence that MMUT is a mitochondrial enzyme.
    action: ACCEPT
    reason: MMUT carries a cleavable mitochondrial transit peptide and is active in the
      mitochondrial matrix; the mitochondrion annotation is correct (matrix is the more
      precise term, annotated separately).
    supported_by:
    - reference_id: PMID:24458
      supporting_text: All of the activity of these two enzymes was demonstrated to be in
        the mitochondria and those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic assignment of the generic parent term catalytic
      activity. True but uninformative relative to the specific methylmalonyl-CoA mutase
      activity annotation.
    action: ACCEPT
    reason: MMUT is an enzyme, so catalytic activity is correct. It is a broad ancestor of
      the specific term GO:0004494; retaining it as a valid, non-misleading electronic
      rollup is acceptable, though it is not core.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to
        succinyl‐CoA
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic assignment (multiple IEA methods, RHEA:22888 / EC 5.4.99.2) of the
      defining molecular function. Concordant with direct experimental evidence.
    action: ACCEPT
    reason: The electronic mapping to methylmalonyl-CoA mutase activity is correct and
      corroborated by human enzyme assays; this is the core function.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: Mitochondrial methylmalonyl‐CoA mutase (MUT, EC 5.4.99.2) catalyzes
        the reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA, requiring
        vitamin B12 (cobalamin) in the form of adenosylcobalamin (AdoCbl) as a cofactor.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location keyword mapping to cytoplasm (SL-0086). MMUT is a
      mitochondrial-matrix enzyme; cytoplasm is imprecise.
    action: MARK_AS_OVER_ANNOTATED
    reason: The cytoplasm keyword derives from the UniProt SUBCELLULAR LOCATION statement
      that lists Cytoplasm alongside Mitochondrion/matrix (from PMID:28943303), but the
      functional, activity-bearing localization is the mitochondrial matrix. Cytoplasm is a
      broad, less-informative term for MMUT.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: All of the activity of these two enzymes was demonstrated to be in
        the mitochondria and those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location keyword mapping to mitochondrion (SL-0173).
      Correct localization for MMUT.
    action: ACCEPT
    reason: MMUT is a mitochondrial protein; the electronic localization is accurate. The
      mitochondrial matrix annotation is the more precise term.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: All of the activity of these two enzymes was demonstrated to be in
        the mitochondria
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt subcellular-location keyword mapping to mitochondrial matrix
      (SL-0170). This is the precise, correct localization of the active enzyme.
    action: ACCEPT
    reason: Direct fractionation studies localize MMUT activity to the mitochondrial matrix
      (loosely bound to the inner membrane-matrix compartment); the electronic annotation
      matches the experimental evidence.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0016853
    label: isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic assignment of the parent term isomerase activity. True
      (MMUT is an intramolecular isomerase/mutase) but broad relative to GO:0004494.
    action: ACCEPT
    reason: MMUT is EC 5.4.99.2, an isomerase; the term is a correct ancestor of the
      specific methylmalonyl-CoA mutase activity term. Valid non-core electronic rollup.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to
        succinyl‐CoA
- term:
    id: GO:0016866
    label: intramolecular transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic assignment of intramolecular transferase activity
      (mutase). Correct intermediate parent of methylmalonyl-CoA mutase activity.
    action: ACCEPT
    reason: Methylmalonyl-CoA mutase is a carbon-skeleton mutase (intramolecular transfer
      of the thioester/carboxyl-bearing group), so GO:0016866 is an accurate ancestor of
      the specific term. Valid non-core electronic rollup.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: catalyzes the reversible isomerisation of l‐methylmalonyl‐CoA to
        succinyl‐CoA
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic assignment of cobalamin binding, based on the B12-binding
      domain signatures. Concordant with the experimental cofactor requirement.
    action: ACCEPT
    reason: MMUT contains a cobalamin-binding domain and requires adenosylcobalamin; the
      electronic annotation matches the direct experimental evidence for cofactor binding.
    supported_by:
    - reference_id: PMID:1978672
      supporting_text: Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent
        enzyme
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro2GO electronic assignment of metal ion binding, reflecting the cobalt
      ion of the bound adenosylcobalamin cofactor.
    action: ACCEPT
    reason: The cofactor adenosylcobalamin contains a cobalt ion that is axially
      coordinated by His627 of MMUT, so metal (cobalt) ion binding is correct, if broad. It
      is captured more informatively by cobalamin binding.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: vitamin B12-dependent methylmalonyl-CoA mutase
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: IntAct IPI (partner MMAA, Q8IVH4). Bare protein binding is uninformative as a
      molecular function; the biologically meaningful apo-MUT:MMAA interaction is captured
      by the homodimerization and positive-regulation-of-GTPase annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Per curation guidance, generic protein binding does not convey a specific
      molecular function and should not be treated as a core annotation. The underlying
      MMAA interaction is real and is documented; it is represented more usefully elsewhere.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: the two proteins interact in vitro and in vivo
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28497574
  qualifier: enables
  review:
    summary: IntAct IPI (partner MMAA, Q8IVH4) from the cblA-type MMA study. Bare protein
      binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is not an informative molecular function. The MUT-MMAA
      interaction it reflects is documented, but is better represented by the
      positive-regulation-of-GTPase-activity annotation.
    supported_by:
    - reference_id: PMID:28497574
      supporting_text: which is stimulated by an interaction with MUT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: IntAct IPI (partner HTT/huntingtin, P42858) from a neurodegenerative-disease
      interactome map. Bare protein binding is uninformative and this is a large-scale
      network interaction of uncertain physiological relevance to MMUT function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding conveys no specific molecular function. This is a
      high-throughput interactome/aggregation screen; the interaction does not inform
      MMUT's characterized enzymatic role.
    supported_by:
    - reference_id: PMID:32814053
      supporting_text: Interactome maps are valuable resources to elucidate protein
        function and disease mechanisms.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: IntAct IPI (partner CRYZ, Q08257) from a proteome-scale interactome study.
      Bare protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is not an informative molecular function. This is a
      large-scale affinity-purification network dataset; the interaction does not inform
      MMUT's core function.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: These networks model the interactome
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: IntAct IPI (partner CRYZ, Q08257) from a multimodal cell-map study. Bare
      protein binding is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding conveys no specific molecular function. This is a
      large-scale mapping dataset; the interaction does not inform MMUT's core function.
    supported_by:
    - reference_id: PMID:40205054
      supporting_text: Multimodal cell maps as a foundation for structural and functional
        genomics.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: IntAct IPI (self, P22033), reflecting the MMUT homodimer. Real but represented
      more informatively by protein homodimerization activity.
    action: KEEP_AS_NON_CORE
    reason: MMUT is a homodimer, so self-association is genuine, but identical protein
      binding is a weaker restatement of the homodimerization annotation; keep as non-core.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: crystallized human MMAA in the GDP-bound form and human MUT in the
        apo, holo, and substrate-bound ternary forms
- term:
    id: GO:1901290
    label: succinyl-CoA biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Electronic assignment of succinyl-CoA biosynthetic process. This is an
      accurate product-oriented description of the MMUT reaction (MM-CoA to succinyl-CoA).
    action: ACCEPT
    reason: MMUT produces succinyl-CoA from methylmalonyl-CoA; the term correctly describes
      the product-forming aspect of its reaction. Complementary to the propionyl-CoA
      catabolic process annotation.
    supported_by:
    - reference_id: PMID:29056341
      supporting_text: It catalyzes the conversion of methylmalonyl-CoA into succinyl-CoA,
        which allows recycling of branched carbon chains from amino acids and lipids into
        the tricarboxylic acid cycle (TCA cycle).
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: EXP
  original_reference_id: PMID:1346616
  qualifier: enables
  review:
    summary: Experimental (EXP) demonstration of methylmalonyl-CoA mutase activity via
      cloning and expression of human MCM and characterization of a cobalamin-affinity
      mutant. Core function.
    action: ACCEPT
    reason: This study expressed human MCM and characterized its catalytic behavior
      (including the G717V mut- mutant with ~1000-fold elevated Km for adenosylcobalamin),
      directly supporting methylmalonyl-CoA mutase activity as the gene's function.
    supported_by:
    - reference_id: PMID:1346616
      supporting_text: an apparent Km (adenosylcobalamin) 1,000-fold higher than normal
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: EXP
  original_reference_id: PMID:25125334
  qualifier: enables
  review:
    summary: Experimental (EXP) characterization of MUT activity across 23 recombinant
      patient missense variants, measuring succinate production from methylmalonyl-CoA.
      Core function.
    action: ACCEPT
    reason: Wild-type and mutant MUT were assayed for conversion of [14C]methylmalonyl-CoA
      to [14C]succinate, directly measuring methylmalonyl-CoA mutase activity and its
      cofactor/substrate kinetics.
    supported_by:
    - reference_id: PMID:25125334
      supporting_text: MUT activity was assayed in crude cell lysates by measuring the
        production of [14C]succinate from [14C]methylmalonyl‐CoA
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: EXP
  original_reference_id: PMID:29056341
  qualifier: enables
  review:
    summary: Experimental (EXP) work using recombinant human MUT reconstituted with coenzyme
      B12; establishes methylmalonyl-CoA mutase activity and its inhibition by itaconyl-CoA.
      Core function.
    action: ACCEPT
    reason: The study characterized recombinant human MUT enzymology (conversion of
      methylmalonyl-CoA to succinyl-CoA using coenzyme B12) and identified itaconyl-CoA as
      a cofactor-inactivating inhibitor, directly supporting the mutase activity.
    supported_by:
    - reference_id: PMID:29056341
      supporting_text: itaconyl-CoA is a cofactor-inactivating, substrate-analog inhibitor
        of the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT)
- term:
    id: GO:1901290
    label: succinyl-CoA biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:1978672
  qualifier: involved_in
  review:
    summary: Direct assay (IDA) of mutase activity producing succinyl-CoA from
      methylmalonyl-CoA. Accurate product-oriented description of the MMUT reaction.
    action: ACCEPT
    reason: Enzyme assays of MCM demonstrated isomerization between methylmalonyl-CoA and
      succinyl-CoA, supporting involvement in succinyl-CoA biosynthesis.
    supported_by:
    - reference_id: PMID:1978672
      supporting_text: an adenosylcobalamin-dependent enzyme that catalyses isomerization
        between methylmalonyl-CoA and succinyl-CoA (3-carboxypropionyl-CoA)
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput (HTP) mitochondrial proteome study placing MMUT among the
      high-confidence mitochondrial proteins (MitoCoP). Consistent with all other evidence.
    action: ACCEPT
    reason: MMUT was classified in the >1,100-protein high-confidence human mitochondrial
      proteome, corroborating its mitochondrial localization.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: defined a mitochondrial high-confidence proteome of >1,100 proteins
        (MitoCoP)
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3322971
  qualifier: located_in
  review:
    summary: Reactome traceable assertion (TAS) placing MMUT in the mitochondrial matrix
      (in the context of defective MUT failing to isomerise L-MM-CoA to succinyl-CoA).
      Correct localization.
    action: ACCEPT
    reason: Reactome curates MMUT as a mitochondrial matrix enzyme; consistent with direct
      fractionation evidence.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IDA
  original_reference_id: PMID:1978672
  qualifier: enables
  review:
    summary: Direct assay (IDA) of methylmalonyl-CoA mutase activity for the cloned enzyme,
      with reaction kinetics similar to the human enzyme. Core function.
    action: ACCEPT
    reason: The enzyme was directly assayed and shown to isomerize methylmalonyl-CoA to
      succinyl-CoA in an adenosylcobalamin-dependent manner, defining the core molecular
      function.
    supported_by:
    - reference_id: PMID:1978672
      supporting_text: catalyses isomerization between methylmalonyl-CoA and succinyl-CoA
        (3-carboxypropionyl-CoA)
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IDA
  original_reference_id: PMID:21138732
  qualifier: enables
  review:
    summary: Direct assay (IDA) of purified recombinant human MCM catalytic activity (and
      its protection/reactivation by MMAA). Core function.
    action: ACCEPT
    reason: Purified recombinant MCM was assayed for its methylmalonyl-CoA mutase reaction
      kinetics, directly establishing the activity.
    supported_by:
    - reference_id: PMID:21138732
      supporting_text: we examined the influence of human MMAA protein on the kinetics of
        the reaction catalyzed by methylmalonyl-CoA mutase (MCM) by testing both purified
        recombinant proteins in vitro
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IDA
  original_reference_id: PMID:24458
  qualifier: enables
  review:
    summary: Direct assay (IDA) of methylmalonyl-CoA mutase activity in hepatic
      mitochondrial fractions (a rapid mutase assay was described). Core function.
    action: ACCEPT
    reason: Methylmalonyl-CoA mutase activity was measured in mitochondrial fractions of
      human and rat liver, directly supporting the molecular function and its mitochondrial
      localization.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: a rapid enzymatic assay for methylmalonyl-CoA mutase was described.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IDA
  original_reference_id: PMID:2453061
  qualifier: enables
  review:
    summary: Direct assay (IDA) of MCM activity constituted by gene transfer of the cloned
      human MCM cDNA into COS cells. Core function.
    action: ACCEPT
    reason: Cells transformed with the human MCM cDNA expressed increased methylmalonyl-CoA
      mutase enzymatic activity, directly demonstrating the function of the cloned gene.
    supported_by:
    - reference_id: PMID:2453061
      supporting_text: Cells transformed with this clone expressed increased levels of MCM
        enzymatic activity.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IDA
  original_reference_id: PMID:28943303
  qualifier: enables
  review:
    summary: Direct assay (IDA) of recombinant human MCM activity, including altered
      kinetics in the presence of MMAA/GTP. Core function.
    action: ACCEPT
    reason: Recombinant hMCM was assayed for its mutase reaction and cofactor kinetics
      (Km/Vmax for methylmalonyl-CoA), directly establishing methylmalonyl-CoA mutase
      activity.
    supported_by:
    - reference_id: PMID:28943303
      supporting_text: Human mitochondrial methylmalonyl-CoA mutase (hMCM) is an isomerase
        that converts methylmalonyl-CoA to succinyl-CoA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:21138732
  qualifier: enables
  review:
    summary: IPI (partner MMAA, Q8IVH4). MUT-MMAA interaction confirmed by yeast two-hybrid.
      Bare protein binding is uninformative as an MF.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding is not an informative molecular function. The real
      MUT-MMAA interaction is documented and is better represented by the
      positive-regulation-of-GTPase-activity annotation.
    supported_by:
    - reference_id: PMID:21138732
      supporting_text: Interaction between MCM and MMAA observed in vitro was confirmed in
        vivo by yeast two-hybrid system.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28943303
  qualifier: enables
  review:
    summary: IPI (partner MMAA, Q8IVH4). Bare protein binding is uninformative as an MF; the
      MUT-MMAA complex is the biologically meaningful interaction.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding conveys no specific molecular function. The MUT-MMAA
      complex formation demonstrated here is better captured by the regulatory and
      localization annotations.
    supported_by:
    - reference_id: PMID:28943303
      supporting_text: restores methylmalonyl-CoA mutase activity through their complex
        formation
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:28943303
  qualifier: located_in
  review:
    summary: Direct-assay (IDA) localization including a cytoplasmic signal in human
      fibroblasts. MMUT is a mitochondrial-matrix enzyme; cytoplasm is imprecise/over-broad.
    action: MARK_AS_OVER_ANNOTATED
    reason: This study reported the in vivo localization and colocalization of hMMAA with
      hMCM in fibroblast mitochondria; the functional pool of MMUT is mitochondrial-matrix.
      Cytoplasm at best reflects a minor apoenzyme/import-intermediate signal and is a less
      informative localization than the mitochondrial matrix annotation.
    supported_by:
    - reference_id: PMID:28943303
      supporting_text: the in vivo localization of hMMAA and its colocalization with hMCM in
        human fibroblasts mitochondria were demonstrated.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:28943303
  qualifier: located_in
  review:
    summary: Direct-assay (IDA) mitochondrial localization of hMCM in human fibroblasts.
      Correct localization.
    action: ACCEPT
    reason: Immunolocalization showed hMCM in fibroblast mitochondria (colocalizing with
      hMMAA), directly supporting the mitochondrial annotation.
    supported_by:
    - reference_id: PMID:28943303
      supporting_text: the in vivo localization of hMMAA and its colocalization with hMCM in
        human fibroblasts mitochondria were demonstrated.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: IDA
  original_reference_id: PMID:24458
  qualifier: located_in
  review:
    summary: Direct-assay (IDA) localization of MMUT activity to the mitochondrial
      inner-membrane/matrix compartment by subcellular fractionation. Precise, core
      localization.
    action: ACCEPT
    reason: All MMUT activity fractionated with mitochondria and was loosely bound to the
      inner membrane-matrix portion, directly establishing the mitochondrial-matrix
      localization.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IDA
  original_reference_id: PMID:1978672
  qualifier: enables
  review:
    summary: Direct assay (IDA) establishing adenosylcobalamin dependence/binding (cofactor
      requirement, Km for adenosylcobalamin). Core cofactor function.
    action: ACCEPT
    reason: The enzyme is adenosylcobalamin-dependent with a defined Km for the cofactor,
      directly supporting cobalamin binding.
    supported_by:
    - reference_id: PMID:1978672
      supporting_text: Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent
        enzyme
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IDA
  original_reference_id: PMID:21138732
  qualifier: enables
  review:
    summary: Direct assay (IDA) of the cobalamin cofactor role, including cofactor oxidation
      during catalysis and its exchange by MMAA. Core cofactor function.
    action: ACCEPT
    reason: The study addressed inactivation due to oxidation of the bound cobalamin and its
      reactivation by cofactor exchange, directly supporting cobalamin binding by MCM.
    supported_by:
    - reference_id: PMID:21138732
      supporting_text: some adenosylcobalamin-dependent enzymes suffer inactivation during
        catalysis due to the oxidation of cobalamin
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IDA
  original_reference_id: PMID:28943303
  qualifier: enables
  review:
    summary: Direct assay (IDA) of the AdoCbl cofactor role, including OH2Cbl formation and
      removal/replacement of damaged cofactor. Core cofactor function.
    action: ACCEPT
    reason: hMCM uses adenosylcobalamin (AdoCbl) and its oxidized inactive form (OH2Cbl) is
      removed via MMAA, directly supporting cobalamin binding.
    supported_by:
    - reference_id: PMID:28943303
      supporting_text: employs highly reactive radicals from its cofactor (adenosylcobalamin,
        AdoCbl)
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: IDA annotation of GTPase activity to MMUT. In this paper the demonstrated GTPase
      is MMAA (the partner protein), whose GTPase activity is modulated by MUT; MUT itself
      is a B12 mutase with no GTPase domain.
    action: UNDECIDED
    reason: The abstract explicitly attributes GTPase activity to MMAA ("MMAA exhibits GTPase
      activity that is modulated by MUT"), and MMUT has no P-loop/GTPase fold, so assigning
      GTPase activity to MMUT appears to be a mis-attribution of the partner's activity.
      However, per curation policy I cannot read the full text to confirm exactly what was
      assayed for MMUT, so I flag this rather than removing an experimental annotation; if
      the assignment cannot be substantiated it should be removed.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: MMAA exhibits GTPase activity that is modulated by MUT
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IDA
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: Direct assay/structure (IDA) with adenosylcobalamin bound to MUT (holo and
      ternary crystal structures), supporting cobalamin binding. Core cofactor function.
    action: ACCEPT
    reason: The crystal structures of human MUT were solved in apo, holo, and
      substrate-bound (ternary) forms with adenosylcobalamin, directly demonstrating
      cobalamin binding (the cobalt is axially coordinated by His627).
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: human MUT in the apo, holo, and substrate-bound ternary forms
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IDA
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: IDA of self-association (MMUT homodimer) from crystallographic subunit analysis.
      Real but a weaker restatement of homodimerization activity.
    action: KEEP_AS_NON_CORE
    reason: MMUT is a homodimer, so identical protein binding is genuine; it duplicates the
      more informative protein homodimerization activity annotation and is not a core
      function.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: they show substantially different dimeric assembly and interaction
- term:
    id: GO:0042803
    label: protein homodimerization activity
  evidence_type: IDA
  original_reference_id: PMID:20876572
  qualifier: enables
  review:
    summary: IDA of homodimerization from the human MUT crystal structure. MMUT is an active
      homodimer; a genuine, structurally supported property.
    action: KEEP_AS_NON_CORE
    reason: The human MUT crystal structures establish a homodimeric assembly. This is a real
      structural property enabling function, but it is ancillary to the core catalytic
      annotation.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: they show substantially different dimeric assembly and interaction,
        compared with their bacterial counterparts
- term:
    id: GO:0043547
    label: positive regulation of GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:20876572
  qualifier: involved_in
  review:
    summary: IDA that MUT modulates (stimulates) the GTPase activity of its partner MMAA.
      A genuine regulatory role, but ancillary to MMUT's core catalytic function.
    action: KEEP_AS_NON_CORE
    reason: The apo-MUT:MMAA interaction modulates MMAA's GTPase activity; this GAP-like
      regulatory role is documented but is peripheral to MMUT's core mutase function.
    supported_by:
    - reference_id: PMID:20876572
      supporting_text: MMAA exhibits GTPase activity that is modulated by MUT
- term:
    id: GO:0043547
    label: positive regulation of GTPase activity
  evidence_type: IDA
  original_reference_id: PMID:28497574
  qualifier: involved_in
  review:
    summary: IDA that MUT stimulates MMAA GTPase activity; loss of this stimulation underlies
      cblA-type MMA. Genuine regulatory role, ancillary to core function.
    action: KEEP_AS_NON_CORE
    reason: MMAA's GTPase activity is stimulated by interaction with MUT, and disease
      mutations reduce this stimulation; the regulatory role is supported but is not MMUT's
      core function.
    supported_by:
    - reference_id: PMID:28497574
      supporting_text: This function of MMAA depends on its GTPase activity, which is
        stimulated by an interaction with MUT.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IMP
  original_reference_id: PMID:28101778
  qualifier: enables
  review:
    summary: IMP evidence from patient loss-of-function missense mutations that reduce MCM
      enzymatic activity in a functional assay. Supports the core mutase function.
    action: ACCEPT
    reason: Eight novel MUT missense mutations reduced MCM protein and activity in a
      permissive assay, genetically implicating MMUT in methylmalonyl-CoA mutase activity.
    supported_by:
    - reference_id: PMID:28101778
      supporting_text: the MCM activity of the mutations was reduced in a permissive assay.
- term:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  evidence_type: IMP
  original_reference_id: PMID:27167370
  qualifier: enables
  review:
    summary: IMP evidence from a large mut-type MMA patient cohort (110 mutations) showing
      reduced MUT protein/activity. Supports the core mutase function.
    action: ACCEPT
    reason: Molecular-genetic characterization of 151 mut-type MMA patients links MUT
      mutations to loss of MUT function (reduced protein and propionate incorporation),
      supporting methylmalonyl-CoA mutase activity as the gene's function.
    supported_by:
    - reference_id: PMID:27167370
      supporting_text: Western blot analysis revealed reduced MUT protein for all 34 cell
        lines (27 mut(0) , seven mut(-) ) tested, suggesting protein instability as a major
        mechanism of deficiency in mut-type MMA.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3159259
  qualifier: located_in
  review:
    summary: Reactome TAS placing MMUT in the mitochondrial matrix (MMAA:MUT binds AdoCbl
      reaction). Correct localization.
    action: ACCEPT
    reason: Reactome curates MMUT (and the MMAA:MUT complex) in the mitochondrial matrix,
      consistent with the experimental localization.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3322135
  qualifier: located_in
  review:
    summary: Reactome TAS placing MMUT in the mitochondrial matrix (Defective MMAA does not
      protect MUT reaction). Correct localization.
    action: ACCEPT
    reason: Reactome consistently curates MMUT in the mitochondrial matrix; consistent with
      the experimental fractionation evidence.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-71010
  qualifier: located_in
  review:
    summary: Reactome TAS placing MMUT in the mitochondrial matrix (MUT isomerises L-MM-CoA
      to SUCC-CoA reaction). Correct localization for the catalytic step.
    action: ACCEPT
    reason: Reactome curates the MUT-catalyzed isomerization of L-methylmalonyl-CoA to
      succinyl-CoA in the mitochondrial matrix, matching the experimental localization.
    supported_by:
    - reference_id: PMID:24458
      supporting_text: those enzymes were shown to be loosely bound to the inner
        membrane-matrix portion of the mitochondria.
- term:
    id: GO:0050667
    label: homocysteine metabolic process
  evidence_type: IDA
  original_reference_id: PMID:20031578
  qualifier: involved_in
  review:
    summary: Annotation derived from a GWAS association of a MUT-locus SNP with plasma
      homocysteine. The paper itself states MUT's catalytic activity is "hardly related to
      homocysteine"; any link is indirect (shared B12 dependence), not a direct molecular
      role of MMUT in homocysteine metabolism.
    action: MARK_AS_OVER_ANNOTATED
    reason: The association is epidemiological/genetic and, per the authors, only indirectly
      related to MMUT function (via competition for vitamin B12 between mitochondrial MUT and
      cytosolic methionine synthase). MMUT does not act on homocysteine or its metabolites,
      so involvement in homocysteine metabolic process is an over-annotation.
    supported_by:
    - reference_id: PMID:20031578
      supporting_text: While its catalytic activity is hardly related to homocysteine, MUT
        has frequently been associated with homocysteine metabolism because it is one of
        three vitamin B 12 dependant enzymes
- term:
    id: GO:0072341
    label: modified amino acid binding
  evidence_type: IDA
  original_reference_id: PMID:20031578
  qualifier: enables
  review:
    summary: Annotation from the same homocysteine GWAS paper. There is no biochemical
      demonstration that MMUT binds a modified amino acid; its characterized ligands are
      methylmalonyl-CoA and adenosylcobalamin.
    action: MARK_AS_OVER_ANNOTATED
    reason: The GWAS study did not assay MMUT binding to any modified amino acid; MMUT's
      substrate is a CoA thioester and its cofactor is a corrinoid, not a modified amino
      acid. This molecular-function annotation does not fit the characterized biochemistry.
    supported_by:
    - reference_id: PMID:20031578
      supporting_text: MUT encodes for the mitochondrial enzyme methylmalonyl-Coa mutase and
        as such, catalyses the isomeration of methylmalonyl-Coa into succinyl-Coa.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: TAS
  original_reference_id: PMID:2567699
  qualifier: located_in
  review:
    summary: Traceable assertion (TAS) of mitochondrial localization; the full-length cDNA
      cloning identified the N-terminal mitochondrial transit peptide. Correct localization.
    action: ACCEPT
    reason: The cloning of full-length human MCM defined its mitochondrial-targeting
      N-terminus (the transit peptide, residues 1-32), supporting mitochondrial
      localization.
    supported_by:
    - reference_id: PMID:2567699
      supporting_text: Cloning of full-length methylmalonyl-CoA mutase from a cDNA library
        using the polymerase chain reaction.
core_functions:
- description: Adenosylcobalamin (coenzyme B12)-dependent methylmalonyl-CoA mutase that
    catalyzes the reversible isomerization of (R)-methylmalonyl-CoA (L-methylmalonyl-CoA) to
    succinyl-CoA, the terminal step of propionyl-CoA catabolism, in the mitochondrial matrix.
  molecular_function:
    id: GO:0004494
    label: methylmalonyl-CoA mutase activity
  directly_involved_in:
  - id: GO:1902859
    label: propionyl-CoA catabolic process
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:25125334
    supporting_text: Mitochondrial methylmalonyl‐CoA mutase (MUT, EC 5.4.99.2) catalyzes the
      reversible isomerisation of l‐methylmalonyl‐CoA to succinyl‐CoA, requiring vitamin B12
      (cobalamin) in the form of adenosylcobalamin (AdoCbl) as a cofactor. In humans, this
      reaction represents an important step in propionate catabolism
- description: Binds adenosylcobalamin (vitamin B12) as an essential catalytic cofactor; the
    cobalt of the corrinoid is axially coordinated by a conserved histidine in the
    C-terminal cobalamin-binding domain, and homolysis of the cobalt-carbon bond generates
    the radical intermediates required for isomerization.
  molecular_function:
    id: GO:0031419
    label: cobalamin binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:1978672
    supporting_text: Methylmalonyl-CoA mutase (MCM) is an adenosylcobalamin-dependent enzyme
      that catalyses isomerization between methylmalonyl-CoA and succinyl-CoA
  - reference_id: PMID:28943303
    supporting_text: employs highly reactive radicals from its cofactor (adenosylcobalamin,
      AdoCbl)
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary
    mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:1346616
  title: Cloning and expression of a mutant methylmalonyl coenzyme A mutase with altered cobalamin
    affinity that causes mut- methylmalonic aciduria.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Human MCM expressed and assayed; characterizes the G717V mut- variant with
      ~1000-fold elevated Km for adenosylcobalamin. Supports mutase activity and cofactor
      binding.
- id: PMID:1978672
  title: Primary structure and activity of mouse methylmalonyl-CoA mutase.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes MCM as an adenosylcobalamin-dependent isomerase (MM-CoA to
      succinyl-CoA); mouse enzyme is 94% identical to human and complements human deficiency.
- id: PMID:20031578
  title: 'Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy
    population: a genome-wide evaluation of 13 974 participants in the Women''s Genome Health
    Study.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: MISCITED
    review_notes: A GWAS associating a MUT-locus SNP with plasma homocysteine. The paper itself
      states MUT's catalytic activity is "hardly related to homocysteine"; it does not support
      direct involvement of MMUT in homocysteine metabolic process or binding of a modified
      amino acid, so the IDA annotations to GO:0050667 and GO:0072341 are over-interpretations.
- id: PMID:20876572
  title: Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase
    and insight into their complex formation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Crystal structures of human MUT (apo/holo/ternary with AdoCbl and malonyl-CoA)
      and MMAA; MUT is a homodimer and forms a GTP-dependent complex with MMAA. Note the GTPase
      activity characterized is MMAA's (modulated by MUT), not MUT's own activity.
- id: PMID:21138732
  title: Protection and reactivation of human methylmalonyl-CoA mutase by MMAA protein.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: In vitro assays of purified recombinant hMCM and hMMAA; MMAA protects/reactivates
      MCM by cofactor exchange via GTP hydrolysis. Supports mutase activity, cobalamin binding,
      and the MMAA interaction.
- id: PMID:24458
  title: Intracellular localization of hepatic propionyl-CoA carboxylase and methylmalonyl-CoA
    mutase in humans and normal and vitamin B12 deficient rats.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Subcellular fractionation localizes all MCM activity to the mitochondria,
      loosely bound to the inner membrane-matrix compartment. Supports mitochondrial-matrix
      localization and mutase activity.
- id: PMID:2453061
  title: 'Molecular cloning of L-methylmalonyl-CoA mutase: gene transfer and analysis of mut
    cell lines.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cloning of human MCM cDNA; gene transfer into COS cells constitutes increased
      MCM enzymatic activity. Supports the identity and mutase activity of the gene product.
- id: PMID:25125334
  title: Functional characterization and categorization of missense mutations that cause methylmalonyl-CoA
    mutase (MUT) deficiency.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; comprehensive enzymology of 23 recombinant MUT variants
      (activity, thermostability, Km for AdoCbl and MM-CoA). Excellent verbatim support for
      the core mutase function, cofactor requirement, and propionate-catabolism context.
- id: PMID:2567699
  title: Cloning of full-length methylmalonyl-CoA mutase from a cDNA library using the polymerase
    chain reaction.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Full-length cloning that defined the N-terminal mitochondrial transit peptide;
      basis of the TAS mitochondrial localization.
- id: PMID:27167370
  title: Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients
    and Identification of 41 Novel Mutations in MUT.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Large mut-type MMA cohort; MUT mutations cause loss of function (reduced
      protein, propionate incorporation). Supports mutase activity via IMP.
- id: PMID:28101778
  title: Eight novel MUT loss-of-function missense mutations in Chinese patients with isolated
    methylmalonic academia.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Functional (HEK293T) assays show patient missense mutations reduce MCM
      protein/activity. Supports mutase activity via IMP.
- id: PMID:28497574
  title: Protein destabilization and loss of protein-protein interaction are fundamental mechanisms
    in cblA-type methylmalonic aciduria.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: MMAA-focused study; MMAA GTPase activity is stimulated by interaction with
      MUT, and cblA-type mutations reduce this. Supports the positive-regulation-of-GTPase
      annotation (MUT as the stimulator of MMAA).
- id: PMID:28943303
  title: Human MMAA induces the release of inactive cofactor and restores methylmalonyl-CoA
    mutase activity through their complex formation.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Recombinant hMCM enzymology; identifies OH2Cbl as the inactivating oxidized
      cofactor and MMAA-mediated cofactor exchange; demonstrates mitochondrial colocalization
      of hMCM and hMMAA. Supports mutase activity, cobalamin binding, and localization.
- id: PMID:29056341
  title: The Human Knockout Gene CLYBL Connects Itaconate to Vitamin B(12).
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Full text available; recombinant human MUT enzymology and clear statement of
      MUT as the mitochondrial-matrix B12-dependent mutase converting MM-CoA to succinyl-CoA;
      identifies itaconyl-CoA as a cofactor-inactivating inhibitor. Strong core-function support.
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers
    Widespread Protein Aggregation in Affected Brains.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput neurodegenerative-disease interactome/aggregation map;
      source of a bare protein-binding IPI (partner HTT). Does not inform MMUT's core function.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Proteome-scale AP-MS interactome dataset; source of a bare protein-binding
      IPI (partner CRYZ). Does not inform MMUT's core function.
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular
    context.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: High-confidence human mitochondrial proteome (MitoCoP) includes MMUT;
      corroborates mitochondrial localization (HTP).
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Large-scale multimodal cell-mapping dataset; source of a bare protein-binding
      IPI (partner CRYZ). Does not inform MMUT's core function.
- id: Reactome:R-HSA-3159259
  title: MMAA:MUT binds AdoCbl
  findings: []
- id: Reactome:R-HSA-3322135
  title: Defective MMAA does not protect MUT
  findings: []
- id: Reactome:R-HSA-3322971
  title: Defective MUT does not isomerise L-MM-CoA to SUCC-CoA
  findings: []
- id: Reactome:R-HSA-71010
  title: MUT isomerises L-MM-CoA to SUCC-CoA
  findings: []