UniProtKB - Q9CZD0 (MMAC_MOUSE)
Protein
Cyanocobalamin reductase / alkylcobalamin dealkylase
Gene
Mmachc
Organism
Mus musculus (Mouse)
Status
Functioni
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. 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. Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol. 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. 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. The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors. Cysteine and homocysteine cannot substitute for glutathione in this reaction.By similarity
Catalytic activityi
- 2 cob(II)alamin—[cyanocobalamin reductase] + 2 hydrogen cyanide + NADP+ = 2 apo—[cyanocobalamin reductase] + 2 cyanocob(III)alamin + H+ + NADPHBy similarityEC:1.16.1.6By similarityThis reaction proceeds in the backwardBy similarity direction.
- an alkylcob(III)alamin + apo--[alkylcobalamin reductase] + glutathione = an S-substituted glutathione + cob(I)alamin—[alkylcobalamin reductase] + H+By similarityEC:2.5.1.151By similarityThis reaction proceeds in the forwardBy similarity direction.
- apo--[alkylcobalamin reductase] + glutathione + methylcob(III)alamin = cob(I)alamin—[alkylcobalamin reductase] + H+ + S-methyl glutathioneBy similarityEC:2.5.1.151By similarityThis reaction proceeds in the forwardBy similarity direction.
- adenosylcob(III)alamin + apo--[alkylcobalamin reductase] + glutathione = cob(I)alamin—[alkylcobalamin reductase] + H+ + S-adenosylglutathioneBy similarityEC:2.5.1.151By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
: adenosylcobalamin biosynthesis Pathwayi
This protein is involved in the pathway adenosylcobalamin biosynthesis, which is part of Cofactor biosynthesis.By similarityView all proteins of this organism that are known to be involved in the pathway adenosylcobalamin biosynthesis and in Cofactor biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 104 | SubstrateBy similarity | 1 | |
Binding sitei | 149 | Substrate; via amide nitrogenBy similarity | 1 | |
Binding sitei | 160 | Substrate; via amide nitrogen and carbonyl oxygenBy similarity | 1 |
GO - Molecular functioni
- cobalamin binding Source: UniProtKB-KW
- cyanocobalamin reductase (cyanide-eliminating) activity Source: UniProtKB
- demethylase activity Source: UniProtKB
- FAD binding Source: UniProtKB
- glutathione binding Source: UniProtKB
- oxidoreductase activity Source: UniProtKB
- protein homodimerization activity Source: MGI
- transferase activity Source: UniProtKB-KW
GO - Biological processi
- cobalamin metabolic process Source: UniProtKB
- demethylation Source: UniProtKB
- glutathione metabolic process Source: UniProtKB
Keywordsi
Molecular function | Oxidoreductase, Transferase |
Ligand | Cobalamin, Cobalt, FAD, Flavoprotein, FMN, NADP |
Enzyme and pathway databases
Reactomei | R-MMU-196741, Cobalamin (Cbl, vitamin B12) transport and metabolism |
UniPathwayi | UPA00148 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyanocobalamin reductase / alkylcobalamin dealkylaseAlternative name(s): |
Gene namesi | Name:MmachcImported |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1914346, Mmachc |
Subcellular locationi
Cytoplasm and Cytosol
- cytosol By similarity
Cytosol
- cytosol Source: UniProtKB-SubCell
Mitochondrion
- mitochondrion Source: MGI
Other locations
- cytoplasm Source: MGI
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Disruption phenotypei
Complete embryonic lethality. All die before 3.5 dpc.1 Publication
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076259 | 1 – 279 | Cyanocobalamin reductase / alkylcobalamin dealkylaseAdd BLAST | 279 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 247 | PhosphoserineBy similarity | 1 | |
Modified residuei | 272 | PhosphoserineBy similarity | 1 | |
Modified residuei | 276 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9CZD0 |
PaxDbi | Q9CZD0 |
PRIDEi | Q9CZD0 |
ProteomicsDBi | 291469 |
PTM databases
iPTMneti | Q9CZD0 |
PhosphoSitePlusi | Q9CZD0 |
Expressioni
Tissue specificityi
Detected in liver and kidney (at protein level) (PubMed:21697092). Detected in embryos (PubMed:24889031).2 Publications
Gene expression databases
Bgeei | ENSMUSG00000028690, Expressed in gastrocnemius and 284 other tissues |
Genevisiblei | Q9CZD0, MM |
Interactioni
Subunit structurei
Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin.
Interacts with LMBRD1 and ABCD4; the interaction ensures the transport of cobalamin from the lysosome to the cytoplasm.
Forms a multiprotein complex with MMADHC, MTR and MTRR; the interaction with MTR could modulate MMACHC-dependent processing of cobalamin. Heterodimer with MMADHC; the interaction might play a role in the regulation of the balance between AdoCbl and MeCbl synthesis.
By similarityGO - Molecular functioni
- protein homodimerization activity Source: MGI
Protein-protein interaction databases
CORUMi | Q9CZD0 |
STRINGi | 10090.ENSMUSP00000030453 |
Miscellaneous databases
RNActi | Q9CZD0, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 115 – 118 | Substrate bindingBy similarity | 4 | |
Regioni | 129 – 131 | Substrate bindingBy similarity | 3 |
Sequence similaritiesi
Belongs to the MMACHC family.Curated
Phylogenomic databases
eggNOGi | KOG4552, Eukaryota |
GeneTreei | ENSGT00390000003464 |
HOGENOMi | CLU_095722_0_0_1 |
InParanoidi | Q9CZD0 |
OMAi | WQDWTYR |
OrthoDBi | 1375709at2759 |
PhylomeDBi | Q9CZD0 |
TreeFami | TF332476 |
Family and domain databases
CDDi | cd12959, MMACHC-like, 1 hit |
InterProi | View protein in InterPro IPR032037, MMACHC |
PANTHERi | PTHR31457, PTHR31457, 1 hit |
Pfami | View protein in Pfam PF16690, MMACHC, 1 hit |
i Sequence
Sequence statusi: Complete.
Q9CZD0-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEPRVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPFPGPTLAF
60 70 80 90 100
LVLSTPAMFD RALKPFLKSC HFQTLRDPVD QCVSYHLRSV TEKFPEVHME
110 120 130 140 150
VIADYEVHPN RRPKILAQTA AHVAGAAYYY QRQDVDADPW GTQHIAGVCI
160 170 180 190 200
HPRFGGWFAI RGVMLLPGIE VPNLPPRKPP DCVPTRAGRI TLLEGFNFHW
210 220 230 240 250
RDWTYRDAVT PEERYSEEQK IYFSTPPAQR LALLGLAQPS EHPSTTSELP
260 270
LSLLTKPQNS RRARSWLSPS VSPPVSPGP
Sequence cautioni
The sequence AAH54756 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAB25214 differs from that shown. Reason: Frameshift.Curated
The sequence BAC39135 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 14 | D → G in BAB28451 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 239 | P → H in BAB28451 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 256 | K → T in BAB28451 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 260 | S → Y in BAB28451 (PubMed:16141072).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK007725 mRNA Translation: BAB25214.1 Frameshift. AK012761 mRNA Translation: BAB28451.1 AK084194 mRNA Translation: BAC39135.1 Different initiation. BC054756 mRNA Translation: AAH54756.1 Different initiation. |
CCDSi | CCDS51278.1 |
RefSeqi | NP_080238.2, NM_025962.3 |
Genome annotation databases
Ensembli | ENSMUST00000030453; ENSMUSP00000030453; ENSMUSG00000028690 |
GeneIDi | 67096 |
KEGGi | mmu:67096 |
UCSCi | uc008uhe.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK007725 mRNA Translation: BAB25214.1 Frameshift. AK012761 mRNA Translation: BAB28451.1 AK084194 mRNA Translation: BAC39135.1 Different initiation. BC054756 mRNA Translation: AAH54756.1 Different initiation. |
CCDSi | CCDS51278.1 |
RefSeqi | NP_080238.2, NM_025962.3 |
3D structure databases
SMRi | Q9CZD0 |
ModBasei | Search... |
Protein-protein interaction databases
CORUMi | Q9CZD0 |
STRINGi | 10090.ENSMUSP00000030453 |
PTM databases
iPTMneti | Q9CZD0 |
PhosphoSitePlusi | Q9CZD0 |
Proteomic databases
EPDi | Q9CZD0 |
PaxDbi | Q9CZD0 |
PRIDEi | Q9CZD0 |
ProteomicsDBi | 291469 |
Protocols and materials databases
ABCDi | Q9CZD0, 1 sequenced antibody |
Antibodypediai | 32641, 377 antibodies |
DNASUi | 67096 |
Genome annotation databases
Ensembli | ENSMUST00000030453; ENSMUSP00000030453; ENSMUSG00000028690 |
GeneIDi | 67096 |
KEGGi | mmu:67096 |
UCSCi | uc008uhe.1, mouse |
Organism-specific databases
CTDi | 25974 |
MGIi | MGI:1914346, Mmachc |
Phylogenomic databases
eggNOGi | KOG4552, Eukaryota |
GeneTreei | ENSGT00390000003464 |
HOGENOMi | CLU_095722_0_0_1 |
InParanoidi | Q9CZD0 |
OMAi | WQDWTYR |
OrthoDBi | 1375709at2759 |
PhylomeDBi | Q9CZD0 |
TreeFami | TF332476 |
Enzyme and pathway databases
UniPathwayi | UPA00148 |
Reactomei | R-MMU-196741, Cobalamin (Cbl, vitamin B12) transport and metabolism |
Miscellaneous databases
BioGRID-ORCSi | 67096, 15 hits in 52 CRISPR screens |
ChiTaRSi | Mmachc, mouse |
PROi | PR:Q9CZD0 |
RNActi | Q9CZD0, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000028690, Expressed in gastrocnemius and 284 other tissues |
Genevisiblei | Q9CZD0, MM |
Family and domain databases
CDDi | cd12959, MMACHC-like, 1 hit |
InterProi | View protein in InterPro IPR032037, MMACHC |
PANTHERi | PTHR31457, PTHR31457, 1 hit |
Pfami | View protein in Pfam PF16690, MMACHC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MMAC_MOUSE | |
Accessioni | Q9CZD0Primary (citable) accession number: Q9CZD0 Secondary accession number(s): Q9D8S7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2006 |
Last sequence update: | January 10, 2006 | |
Last modified: | April 7, 2021 | |
This is version 114 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families