| Tag | Content |
|---|---|
| Uniprot ID | Q9Y4U1; Q5T157; Q9BRQ7; |
| Entrez ID | 25974 |
| Genbank protein ID | CAB45693.2; AAH06122.3; |
| Genbank nucleotide ID | NM_001330540.1; NM_015506.2; |
| Ensembl protein ID | ENSP00000383840 |
| Ensembl nucleotide ID | ENSG00000132763 |
| Gene name | Cyanocobalamin reductase / alkylcobalamin dealkylase |
| Gene symbol | MMACHC |
| Organism | Homo sapiens |
| NCBI taxa ID | 9606 |
| Cleft type | |
| Developmental stage | |
| Data sources | Homology search |
| Reference | |
| Functional description | 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). |
| Sequence | MEPKVAELKQ KIEDTLCPFG FEVYPFQVAW YNELLPPAFH LPLPGPTLAF LVLSTPAMFD 60 RALKPFLQSC HLRMLTDPVD QCVAYHLGRV RESLPELQIE IIADYEVHPN RRPKILAQTA 120 AHVAGAAYYY QRQDVEADPW GNQRISGVCI HPRFGGWFAI RGVVLLPGIE VPDLPPRKPH 180 DCVPTRADRI ALLEGFNFHW RDWTYRDAVT PQERYSEEQK AYFSTPPAQR LALLGLAQPS 240 EKPSSPSPDL PFTTPAPKKP GNPSRARSWL SPRVSPPASP GP 282 |
Abbreviation :
CLO : cleft lip only. CPO : cleft palate only.
CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.