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Details on Person UniProt:Q9Y4U1 MMACHC
| Class:Id | ReferenceGeneProduct:237523 |
|---|---|
| _chainChangeLog | chain:1-282 added on Sat February 7 2015 |
| _displayName | UniProt:Q9Y4U1 MMACHC |
| _timestamp | 2026-02-20 22:56:58 |
| chain | chain:1-282 |
| checksum | 3A7E6BC774CB5D17 |
| comment | FUNCTION Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate (PubMed:18779575, PubMed:19700356, PubMed:21697092, PubMed:25809485). Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle (PubMed:19801555). Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol (PubMed:25535791). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:21071249, PubMed:27771510). Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether (PubMed:19801555, PubMed:21697092, PubMed:22642810, PubMed:25809485). The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors (PubMed:19801555). Cysteine and homocysteine cannot substitute for glutathione in this reaction (PubMed:19801555).CATALYTIC ACTIVITY 2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP(+) = 2 cyanocob(III)alamin + 2 apo-[cyanocobalamin reductase] + NADPH + H(+)CATALYTIC ACTIVITY apo-[alkylcobalamin reductase] + an R-cob(III)alamin + glutathione = cob(I)alamin-[alkylcobalamin reductase] + an S-substituted glutathione + H(+)CATALYTIC ACTIVITY apo-[alkylcobalamin reductase] + methylcob(III)alamin + glutathione = S-methyl glutathione + cob(I)alamin-[alkylcobalamin reductase] + H(+)CATALYTIC ACTIVITY apo-[alkylcobalamin reductase] + adenosylcob(III)alamin + glutathione = S-adenosylglutathione + cob(I)alamin-[alkylcobalamin reductase] + H(+)COFACTOR Can utilize both FAD and FMN.BIOPHYSICOCHEMICAL PROPERTIES kcat is 11.7 h(-1) for the dealkylation of methylcobalamin (MeCbl) (PubMed:19801555). kcat is 0.006 h(-1) for the dealkylation of 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:19801555).SUBUNIT Monomer in the absence of bound substrate (PubMed:21697092, PubMed:22642810). Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin (PubMed:22642810). Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm (PubMed:25535791). Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin (PubMed:27771510). Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis (PubMed:21071249, PubMed:23415655, PubMed:26483544).SUBCELLULAR LOCATION Widely expressed. Expressed at higher level in fetal liver. Also expressed in spleen, lymph node, thymus and bone marrow. Weakly or not expressed in peripheral blood leukocytes.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the MMACHC family. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: Cyanocobalamin reductase / alkylcobalamin dealkylase alternativeName: Alkylcobalamin:glutathione S-alkyltransferase ecNumber evidence="5 8 9 13"2.5.1.151 alternativeName: fullName evidence="18 20"CblC alternativeName: Cyanocobalamin reductase (cyanide-eliminating) ecNumber evidence="3 4 8 13"1.16.1.6 alternativeName: fullName evidence="16"Methylmalonic aciduria and homocystinuria type C protein shortName: MMACHC |
| geneName | MMACHC |
| identifier | Q9Y4U1 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Cobalamin Cobalt Cytoplasm Disease variant FAD Flavoprotein FMN NADP Oxidoreductase Phosphoprotein Proteomics identification Reference proteome Transferase |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MMACHC |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9001277] ENSEMBL:ENSG00000132763 MMACHC [Homo sapiens] |
| secondaryIdentifier | MMAC_HUMAN Q5T157 Q9BRQ7 |
| sequenceLength | 282 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:2980949] MMACHC [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3318572] MMACHC R132* [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3318593] MMACHC R111* [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3318604] MMACHC R91Kfs*14 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3318613] MMACHC R161Q [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:3928672] MMACHC W203* [cytosol] [Homo sapiens] |
| (referenceSequence) | [ReplacedResidue:3318565] L-leucine 97 replaced with L-alanine [ReplacedResidue:3318568] L-isoleucine 99 replaced with L-aspartic acid [ReplacedResidue:3318569] L-alanine 103 replaced with L-cysteine [NonsenseMutation:3318570] Nonsense mutation at L-arginine 132 [ReplacedResidue:3318579] L-isoleucine 101 replaced with L-asparagine [ReplacedResidue:3318580] L-leucine 94 replaced with L-proline [ReplacedResidue:3318581] L-arginine 91 replaced with L-lysine [ReplacedResidue:3318585] L-serine 93 replaced with L-glutamic acid [ReplacedResidue:3318586] L-glutamic acid 100 replaced with L-arginine [ReplacedResidue:3318588] L-glutamine 98 replaced with L-alanine |
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No pathways have been reviewed or authored by UniProt:Q9Y4U1 MMACHC (237523)
