UniProtKB - Q5ZL21 (MMAC_CHICK)
Protein
Cyanocobalamin reductase / alkylcobalamin dealkylase
Gene
MMACHC
Organism
Gallus gallus (Chicken)
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 | 101 | SubstrateBy similarity | 1 | |
Binding sitei | 146 | Substrate; via amide nitrogenBy similarity | 1 | |
Binding sitei | 157 | 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
- 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
UniPathwayi | UPA00148 |
Names & Taxonomyi
Protein namesi | Recommended name: Cyanocobalamin reductase / alkylcobalamin dealkylaseAlternative name(s): |
Gene namesi | Name:MMACHC ORF Names:RCJMB04_8d5 |
Organismi | Gallus gallus (Chicken) |
Taxonomic identifieri | 9031 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Archelosauria › Archosauria › Dinosauria › Saurischia › Theropoda › Coelurosauria › Aves › Neognathae › Galloanserae › Galliformes › Phasianidae › Phasianinae › Gallus |
Proteomesi |
|
Subcellular locationi
Cytoplasm and Cytosol
- cytosol By similarity
Keywords - Cellular componenti
CytoplasmPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000076260 | 1 – 238 | Cyanocobalamin reductase / alkylcobalamin dealkylaseAdd BLAST | 238 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q5ZL21 |
Interactioni
Subunit structurei
Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin. Heterodimer with MMADHC.
By similarityProtein-protein interaction databases
STRINGi | 9031.ENSGALP00000016616 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 112 – 115 | Substrate bindingBy similarity | 4 | |
Regioni | 126 – 128 | Substrate bindingBy similarity | 3 |
Sequence similaritiesi
Belongs to the MMACHC family.Curated
Phylogenomic databases
eggNOGi | KOG4552, Eukaryota |
InParanoidi | Q5ZL21 |
OrthoDBi | 1375709at2759 |
PhylomeDBi | Q5ZL21 |
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.
Q5ZL21-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEERVAERLH GALGPLGFEV HAFKVGWYNA VLQPAFHLPY PDDTLAFVVL
60 70 80 90 100
STPSMFDKAL KPFVNKERLK IIRDPVDQCV SHHLSSVKEI FPDQKVDVIF
110 120 130 140 150
DYEILPSRRP KFLAQTAAHV AGAAYYYQRK DVKLDPWGEK KIFGVCIHPK
160 170 180 190 200
YGGWFAIRGL LLFPDVQVPF LEQSAPVDCV STEEKRTELL ELFNFHWQDG
210 220 230
RYRDIIEVKE RYSEEQKTYF STPPAERFRL LGLTRFTE
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ719913 mRNA Translation: CAG31572.1 |
RefSeqi | NP_001026452.1, NM_001031281.1 |
Genome annotation databases
GeneIDi | 424597 |
KEGGi | gga:424597 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AJ719913 mRNA Translation: CAG31572.1 |
RefSeqi | NP_001026452.1, NM_001031281.1 |
3D structure databases
SMRi | Q5ZL21 |
ModBasei | Search... |
Protein-protein interaction databases
STRINGi | 9031.ENSGALP00000016616 |
Proteomic databases
PaxDbi | Q5ZL21 |
Genome annotation databases
GeneIDi | 424597 |
KEGGi | gga:424597 |
Organism-specific databases
CTDi | 25974 |
Phylogenomic databases
eggNOGi | KOG4552, Eukaryota |
InParanoidi | Q5ZL21 |
OrthoDBi | 1375709at2759 |
PhylomeDBi | Q5ZL21 |
Enzyme and pathway databases
UniPathwayi | UPA00148 |
Miscellaneous databases
PROi | PR:Q5ZL21 |
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_CHICK | |
Accessioni | Q5ZL21Primary (citable) accession number: Q5ZL21 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2006 |
Last sequence update: | November 23, 2004 | |
Last modified: | April 7, 2021 | |
This is version 63 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families