MMAC_CHICK
ID MMAC_CHICK Reviewed; 238 AA.
AC Q5ZL21;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Cyanocobalamin reductase / alkylcobalamin dealkylase;
DE AltName: Full=Alkylcobalamin:glutathione S-alkyltransferase;
DE EC=2.5.1.151 {ECO:0000250|UniProtKB:Q9Y4U1};
DE AltName: Full=CblC;
DE AltName: Full=Cyanocobalamin reductase (cyanide-eliminating);
DE EC=1.16.1.6 {ECO:0000250|UniProtKB:Q9Y4U1};
DE AltName: Full=Methylmalonic aciduria and homocystinuria type C protein;
DE Short=MMACHC;
GN Name=MMACHC; ORFNames=RCJMB04_8d5;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
CC -!- FUNCTION: Cobalamin (vitamin B12) cytosolic chaperone that catalyzes
CC the reductive decyanation of cyanocob(III)alamin (cyanocobalamin,
CC CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as
CC cofactors and NADPH as cosubstrate. Cyanocobalamin constitutes the
CC inactive form of vitamin B12 introduced from the diet, and is converted
CC into the active cofactors methylcobalamin (MeCbl) involved in
CC methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl)
CC involved in the TCA cycle. Forms a complex with the lysosomal
CC transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin
CC across the lysosomal membrane into the cytosol. The processing of
CC cobalamin in the cytosol occurs in a multiprotein complex composed of
CC at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR
CC (methionine synthase) which may contribute to shuttle safely and
CC efficiently cobalamin towards MTR in order to produce methionine. Also
CC acts as a glutathione transferase by catalyzing the dealkylation of the
CC alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of
CC glutathione for nucleophilic displacement to generate cob(I)alamin and
CC the corresponding glutathione thioether. The conversion of incoming
CC MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to
CC meet the cellular needs for both cofactors. Cysteine and homocysteine
CC cannot substitute for glutathione in this reaction.
CC {ECO:0000250|UniProtKB:Q9Y4U1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 cob(II)alamin-[cyanocobalamin reductase] + 2 hydrogen
CC cyanide + NADP(+) = 2 apo-[cyanocobalamin reductase] + 2
CC cyanocob(III)alamin + H(+) + NADPH; Xref=Rhea:RHEA:16113, Rhea:RHEA-
CC COMP:14717, Rhea:RHEA-COMP:14718, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16304, ChEBI:CHEBI:17439, ChEBI:CHEBI:18407,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:83228; EC=1.16.1.6;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:16115;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an R-cob(III)alamin + apo-[alkylcobalamin reductase] +
CC glutathione = an S-substituted glutathione + cob(I)alamin-
CC [alkylcobalamin reductase] + H(+); Xref=Rhea:RHEA:40719, Rhea:RHEA-
CC COMP:14730, Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228,
CC ChEBI:CHEBI:90779, ChEBI:CHEBI:140785; EC=2.5.1.151;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40720;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=apo-[alkylcobalamin reductase] + glutathione +
CC methylcob(III)alamin = cob(I)alamin-[alkylcobalamin reductase] + H(+)
CC + S-methyl glutathione; Xref=Rhea:RHEA:63132, Rhea:RHEA-COMP:14730,
CC Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378, ChEBI:CHEBI:28115,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228,
CC ChEBI:CHEBI:141467; EC=2.5.1.151;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63133;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosylcob(III)alamin + apo-[alkylcobalamin reductase] +
CC glutathione = cob(I)alamin-[alkylcobalamin reductase] + H(+) + S-
CC adenosylglutathione; Xref=Rhea:RHEA:63136, Rhea:RHEA-COMP:14730,
CC Rhea:RHEA-COMP:14731, ChEBI:CHEBI:15378, ChEBI:CHEBI:18408,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:60488, ChEBI:CHEBI:83228,
CC ChEBI:CHEBI:146184; EC=2.5.1.151;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63137;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4U1};
CC Note=Can utilize both FAD and FMN. {ECO:0000250|UniProtKB:Q9Y4U1};
CC -!- SUBUNIT: Monomer in the absence of bound substrate. Homodimer;
CC dimerization is triggered by binding to FMN or adenosylcobalamin.
CC Heterodimer with MMADHC. {ECO:0000250|UniProtKB:Q9Y4U1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q9Y4U1}.
CC -!- SIMILARITY: Belongs to the MMACHC family. {ECO:0000305}.
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DR EMBL; AJ719913; CAG31572.1; -; mRNA.
DR RefSeq; NP_001026452.1; NM_001031281.1.
DR AlphaFoldDB; Q5ZL21; -.
DR SMR; Q5ZL21; -.
DR STRING; 9031.ENSGALP00000016616; -.
DR PaxDb; Q5ZL21; -.
DR GeneID; 424597; -.
DR KEGG; gga:424597; -.
DR CTD; 25974; -.
DR VEuPathDB; HostDB:geneid_424597; -.
DR eggNOG; KOG4552; Eukaryota.
DR InParanoid; Q5ZL21; -.
DR OrthoDB; 1375709at2759; -.
DR PhylomeDB; Q5ZL21; -.
DR PRO; PR:Q5ZL21; -.
DR Proteomes; UP000000539; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0031419; F:cobalamin binding; IEA:UniProtKB-KW.
DR GO; GO:0033787; F:cyanocobalamin reductase (cyanide-eliminating) activity; ISS:UniProtKB.
DR GO; GO:0032451; F:demethylase activity; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB.
DR GO; GO:0043295; F:glutathione binding; ISS:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0009235; P:cobalamin metabolic process; ISS:UniProtKB.
DR GO; GO:0070988; P:demethylation; ISS:UniProtKB.
DR GO; GO:0006749; P:glutathione metabolic process; ISS:UniProtKB.
DR CDD; cd12959; MMACHC-like; 1.
DR InterPro; IPR032037; MMACHC.
DR PANTHER; PTHR31457; PTHR31457; 1.
DR Pfam; PF16690; MMACHC; 1.
PE 2: Evidence at transcript level;
KW Cobalamin; Cobalt; Cytoplasm; FAD; Flavoprotein; FMN; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..238
FT /note="Cyanocobalamin reductase / alkylcobalamin
FT dealkylase"
FT /id="PRO_0000076260"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4U1"
FT BINDING 112..115
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4U1"
FT BINDING 126..128
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4U1"
FT BINDING 146
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4U1"
FT BINDING 157
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4U1"
SQ SEQUENCE 238 AA; 27637 MW; 2965A652A61AB72B CRC64;
MEERVAERLH GALGPLGFEV HAFKVGWYNA VLQPAFHLPY PDDTLAFVVL STPSMFDKAL
KPFVNKERLK IIRDPVDQCV SHHLSSVKEI FPDQKVDVIF DYEILPSRRP KFLAQTAAHV
AGAAYYYQRK DVKLDPWGEK KIFGVCIHPK YGGWFAIRGL LLFPDVQVPF LEQSAPVDCV
STEEKRTELL ELFNFHWQDG RYRDIIEVKE RYSEEQKTYF STPPAERFRL LGLTRFTE
