MMAB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008817 corrinoid adenosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred corrinoid (cob(I)alamin) adenosyltransferase activity, the established core molecular function of MMAB. This matches the direct experimental evidence and the UniProt catalytic activity assignment (Rhea:56796). Reason: This is the correct core molecular function and is corroborated by multiple independent experimental annotations (EXP/IDA) plus the ARBA electronic assignment; the IBA is at the right level of specificity. Supporting Evidence: PMID:12514191 ATP:cob(I)alamin adenosyltransferase (ATR) catalyzes the terminal step in the conversion of cobalamins into Ado-B12.
GO:0005739 mitochondrion	IEA GO_REF:0000044	ACCEPT	Summary: Electronic assignment of mitochondrial localization from the UniProt Subcellular Location vocabulary. MMAB carries a cleaved N-terminal mitochondrial transit peptide (residues 1-32) and acts in the mitochondrial matrix. Reason: Correct compartment; consistent with the UniProt SUBCELLULAR LOCATION (Mitochondrion), the predicted transit peptide, and high-confidence mitochondrial proteomics. The more specific matrix location is captured by separate annotations. Supporting Evidence: PMID:33797888 In the matrix, adenosyltransferase (ATR, also known as MMAB or CblB) and CblA (or MMAA), a G-protein chaperone, are recruited for the synthesis and delivery of AdoCbl to the target enzyme, MCM (or Mut)
GO:0008817 corrinoid adenosyltransferase activity	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning electronic assignment of the core corrinoid adenosyltransferase activity, consistent with the experimental and phylogenetic evidence. Reason: Correct core molecular function; the ARBA mapping agrees with EXP/IDA/IBA evidence. Supporting Evidence: PMID:12514191 ATP:cob(I)alamin adenosyltransferase (ATR) catalyzes the terminal step in the conversion of cobalamins into Ado-B12.
GO:0009235 cobalamin metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: Electronic assignment of involvement in cobalamin metabolism. MMAB performs the terminal step of adenosylcobalamin (coenzyme B12) synthesis, so it is correctly placed in cobalamin metabolic process. Reason: Correct biological process at an appropriate grain for a human enzyme (humans do not perform de novo corrin ring biosynthesis; MMAB acts in cofactor conversion/tailoring of dietary B12). Supporting Evidence: PMID:12514191 ATP:cob(I)alamin adenosyltransferase (ATR) catalyzes the terminal step in the conversion of cobalamins into Ado-B12.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a large-scale interactome perturbation study (IntAct interactor CBY2, Q8NA61-2). Provides no specific information about MMAB molecular function. Reason: Uninformative generic protein binding derived from a high-throughput screen; the cited paper does not characterize MMAB function. Per curation policy, retained but marked as over-annotated rather than removed.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a neurodegenerative-disease interactome map (IntAct interactors CALR/P27797, DLST/P36957, NEK7/Q8TDX7, OPTN/Q96CV9). Uninformative for molecular function. Reason: Generic protein binding from a large-scale two-hybrid/AP-MS network; no functional MMAB characterization in the source. Retained but marked as over-annotated per policy.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a proteome-scale interactome network (IntAct interactor DBT/P11182). Notably DBT (a mitochondrial 2-oxo acid dehydrogenase E2 subunit) is a plausible matrix neighbour, but the annotation itself conveys no specific function. Reason: Generic protein binding from a high-throughput interactome; uninformative molecular-function term. Retained but marked as over-annotated per policy.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Bare protein binding from a multimodal cell-map study (IntAct interactor DBT/P11182). Duplicates the DBT interaction and conveys no specific molecular function. Reason: Generic protein binding from a large-scale mapping resource; uninformative term. Retained but marked as over-annotated per policy.
GO:0009235 cobalamin metabolic process	TAS Reactome:R-HSA-9759218	ACCEPT	Summary: Reactome-curated involvement of MMAB in cobalamin metabolism, reflecting its role in the AdoCbl branch of the intracellular cobalamin trafficking/processing pathway. Reason: Correct biological process, well supported by the enzyme's characterized role in producing the AdoCbl cofactor from dietary cobalamin. Supporting Evidence: PMID:33797888 Mutations in any of these three proteins lead to isolated methylmalonic aciduria while sparing the MeCbl branch of the trafficking pathway.
GO:0008817 corrinoid adenosyltransferase activity	EXP PMID:15913339 Spectroscopic evidence for the formation of a four-coordinat...	ACCEPT	Summary: Experimental (spectroscopic) study of human ATR (MMAB) demonstrating cobalamin binding and the ATP-dependent coordination chemistry that underlies its adenosyltransferase function, forming a four-coordinate Co2+ cobalamin species that raises the redox potential toward the physiological range to enable cob(I)alamin formation prior to adenosylation. Reason: Direct experimental evidence on the human enzyme for its corrinoid adenosyltransferase mechanism; supports the core molecular function. Supporting Evidence: PMID:15913339 The human adenosyltransferase hATR converts exogenous cobalamin into coenzyme B12 by transferring the adenosyl group from cosubstrate ATP to a transiently formed Co1+cobalamin (Co1+Cbl) species.
GO:0008817 corrinoid adenosyltransferase activity	EXP PMID:30282455 Sacrificial Cobalt-Carbon Bond Homolysis in Coenzyme B(12) a...	ACCEPT	Summary: Experimental study confirming that human ATR (MMAB) synthesizes AdoCbl by adenosylation of cob(I)alamin by ATP and directly delivers the product to methylmalonyl-CoA mutase; also demonstrates the sacrificial Co-C bond homolysis cofactor-conservation activity. Reason: Direct experimental evidence on the human enzyme supporting corrinoid adenosyltransferase activity (the AdoCbl-synthesizing reaction). Supporting Evidence: PMID:30282455 AdoCbl is synthesized by adenosyltransferase (ATR), which catalyzes the adenosylation of cob(I)alamin by ATP in a direct nucleophilic displacement reaction that leads to cobalt−carbon (Co−C) bond formation yielding AdoCbl and inorganic triphosphate
GO:0008817 corrinoid adenosyltransferase activity	EXP PMID:33797888 Redox-Linked Coordination Chemistry Directs Vitamin B(12) Tr...	ACCEPT	Summary: Review/primary account (Banerjee lab) describing the human adenosyltransferase (ATR/MMAB) homotrimer that catalyses adenosylation of cob(I)alamin by ATP, with detailed loop-dynamics and redox-linked coordination chemistry underlying the reaction. Reason: Supports the core corrinoid adenosyltransferase activity of the human enzyme. Supporting Evidence: PMID:33797888 ATR, an 81 kDa homotrimer with active sites housed at the subunit interfaces (Fig. 5A),62 catalyzes the adenosylation of cob(I)alamin by ATP.
GO:0008817 corrinoid adenosyltransferase activity	TAS Reactome:R-HSA-3322125	ACCEPT	Summary: Reactome-curated corrinoid adenosyltransferase activity of MMAB, corresponding to the reaction MMAB adenosylates cob(I)alamin. Consistent with all experimental evidence. Reason: Correct core molecular function, curated by Reactome and matching the experimental record. Supporting Evidence: PMID:12514191 ATP:cob(I)alamin adenosyltransferase (ATR) catalyzes the terminal step in the conversion of cobalamins into Ado-B12.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	ACCEPT	Summary: High-throughput assignment of MMAB to the mitochondrion from a quantitative high-confidence human mitochondrial proteome. Consistent with the transit peptide and matrix function. Reason: Correct compartment, corroborating the UniProt localization and the enzyme's matrix role. Supporting Evidence: PMID:33797888 In the matrix, adenosyltransferase (ATR, also known as MMAB or CblB) and CblA (or MMAA), a G-protein chaperone, are recruited for the synthesis and delivery of AdoCbl to the target enzyme, MCM (or Mut)
GO:0009235 cobalamin metabolic process	IDA PMID:12514191 Identification of the human and bovine ATP:Cob(I)alamin aden...	ACCEPT	Summary: Direct experimental evidence placing MMAB in cobalamin metabolism: the human ATR cDNA complemented an ATR-deficient bacterial mutant and its dysregulation was shown in cblB methylmalonic aciduria cell lines, establishing MMAB as the enzyme performing the terminal conversion of cobalamin to coenzyme B12. Reason: Well-supported biological-process annotation from the defining functional study of MMAB. Supporting Evidence: PMID:12514191 We propose that inborn errors in the human ATR gene identified here result in methylmalonyl aciduria.
GO:0016765 transferase activity, transferring alkyl or aryl (other than methyl) groups	IDA PMID:12514191 Identification of the human and bovine ATP:Cob(I)alamin aden...	MODIFY	Summary: Direct evidence that MMAB is a transferase transferring a (non-methyl) alkyl group — the 5'-deoxyadenosyl group — but this is a parent term of the specific corrinoid adenosyltransferase activity (GO:0008817 is a subclass of GO:0016765). The specific term is warranted. Reason: Correct in essence but too general: the transferred group is specifically the deoxyadenosyl moiety onto cob(I)alamin, which is captured precisely by GO:0008817 corrinoid adenosyltransferase activity (an is-a descendant of GO:0016765). Replace with the specific term. Proposed replacements: corrinoid adenosyltransferase activity Supporting Evidence: PMID:12514191 ATP:cob(I)alamin adenosyltransferase (ATR) catalyzes the terminal step in the conversion of cobalamins into Ado-B12.
GO:0009235 cobalamin metabolic process	TAS PMID:28497574 Protein destabilization and loss of protein-protein interact...	ACCEPT	Summary: Traceable author statement placing MMAB in cobalamin metabolism: the paper describes MMAB as the adenosyltransferase that generates AdoCbl for delivery to methylmalonyl-CoA mutase. Reason: Correct biological process; the source explicitly frames MMAB as the AdoCbl-generating enzyme in the mitochondrial cobalamin pathway. Supporting Evidence: PMID:28497574 MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT).
GO:0031419 cobalamin binding	IDA PMID:28497574 Protein destabilization and loss of protein-protein interact...	ACCEPT	Summary: Direct evidence that MMAB binds cobalamin (adenosylcobalamin). MMAB binds the cofactor in a base-off state and holds the AdoCbl product prior to hand-off to the mutase; UniProt cites this reference for adenosylcobalamin-binding. Reason: Cobalamin binding is an integral, experimentally supported feature of MMAB's function as a B12 adenosyltransferase and escort. Supporting Evidence: PMID:28497574 MMAA regulates the incorporation of the cofactor adenosylcobalamin (AdoCbl), generated from the MMAB adenosyltransferase, into the destination enzyme methylmalonyl-CoA mutase (MUT).
GO:0008817 corrinoid adenosyltransferase activity	IDA PMID:12514191 Identification of the human and bovine ATP:Cob(I)alamin aden...	ACCEPT	Summary: Direct experimental demonstration of corrinoid (cob(I)alamin) adenosyltransferase activity for the human enzyme: recombinant human ATR produced measurable ATR activity and complemented an ATR-deficient bacterial mutant for Ado-B12-dependent growth. Reason: Gold-standard direct assay of the core molecular function on the human protein. Supporting Evidence: PMID:12514191 Enzyme assays showed that expression strains produced 87 and 98 nmol/min/mg ATR activity, respectively.
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-3322125	ACCEPT	Summary: Reactome-curated mitochondrial matrix localization for MMAB, the compartment where AdoCbl is synthesized and delivered to methylmalonyl-CoA mutase. Reason: Correct and appropriately specific subcellular location, consistent with the matrix role of the AdoCbl-synthesis/delivery machinery. Supporting Evidence: PMID:33797888 In the matrix, adenosyltransferase (ATR, also known as MMAB or CblB) and CblA (or MMAA), a G-protein chaperone, are recruited for the synthesis and delivery of AdoCbl to the target enzyme, MCM (or Mut)
GO:0005759 mitochondrial matrix	TAS Reactome:R-HSA-3159253	ACCEPT	Summary: Reactome-curated mitochondrial matrix localization (from the MMAB adenosylates cob(I)alamin reaction). Duplicate compartment assignment; correct. Reason: Correct specific location; consistent with the enzyme's matrix function. Supporting Evidence: PMID:33797888 In the matrix, adenosyltransferase (ATR, also known as MMAB or CblB) and CblA (or MMAA), a G-protein chaperone, are recruited for the synthesis and delivery of AdoCbl to the target enzyme, MCM (or Mut)
GO:0005524 ATP binding	IDA PMID:17176040 Structure of ATP-bound human ATP:cobalamin adenosyltransfera...	NEW	Summary: ATP binding is a defining feature of MMAB: it is the adenosyl-donor cosubstrate and ATP binding also organizes the high-affinity cobalamin pocket and gates cofactor delivery to the mutase. The ATP-bound human ATR crystal structure (PDB 2IDX) and UniProt ATP-binding features (residues 60-63, 68-69, 78, 190-194, 214) directly establish this. Present in UniProt (GO:0005524 IEA:UniProtKB-KW) but absent from the current GOA TSV, so added here. Reason: Structurally and biochemically established, functionally central molecular function (ATP is the adenosyl donor) that is missing from the GOA set; added with the ATP-bound structure as evidence. Supporting Evidence: PMID:33797888 ATP binding organizes a high affinity cob(II)alamin pocket in human ATR.

Gene Description

Existing Annotations Review

Core Functions

Catalyses the terminal step of adenosylcobalamin (coenzyme B12) synthesis, transferring the 5'-deoxyadenosyl group from ATP to reduced cob(I)alamin to produce adenosylcob(III)alamin, and uses ATP as the adenosyl donor.

Binds cobalamin (in a base-off state) and, in an ATP-dependent manner, holds the AdoCbl product and delivers it directly to methylmalonyl-CoA mutase, functioning as a cobalamin-binding cofactor escort in the mitochondrial matrix.

References

📚 Additional Documentation

Notes

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