Cyanocobalamin reductase / alkylcobalamin dealkylase (Alkylcobalamin:glutathione S-alkyltransferase) (EC 2.5.1.151) (CblC) (Cyanocobalamin reductase (cyanide-eliminating)) (EC 1.16.1.6) (Methylmalonic aciduria and homocystinuria type C protein) (MMACHC)
1_MEPKV 6_ AELKQ 11_ KIEDT 16_ LCPFG 21_ FEVYP 26_ FQVAW 31_ YNELL 36_ PPAFH 41_ LPLPG 46_ PTLAF 51_ LVLST 56_ PAMFD 61_ RALKP 66_ FLQSC 71_ HLRML 76_ TDPVD 81_ QCVAY 86_ HLGRV 91_ RESLP 96_ ELQIE 101_ IIADY 106_ EVHPN 111_ RRPKI 116_ LAQTA 121_ AHVAG 126_ AAYYY 131_ QRQDV 136_ EADPW 141_ GNQRI 146_ SGVCI 151_ HPRFG 156_ GWFAI 161_ RGVVL 166_ LPGIE 171_ VPDLP 176_ PRKPH 181_ DCVPT 186_ RADRI 191_ ALLEG 196_ FNFHW 201_ RDWTY 206_ RDAVT 211_ PQERY 216_ SEEQK 221_ AYFST 226_ PPAQR 231_ LALLG 236_ LAQPS 241_ EKPSS 246_ PSPDL 251_ PFTTP 256_ APKKP 261_ GNPSR 266_ ARSWL 271_ SPRVS 276_PPASP
1: 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)