MMACHC
entrez
25974
canonical
uniprot
Q9Y4U1
canonical
ensembl
ENSG00000132763
resolver
ensp
ENSP00000383840
resolver
ensp
ENSP00000478859
resolver
enst
ENST00000401061
resolver
enst
ENST00000616135
resolver
genesymbol
MMACHC
resolver
hgnc
HGNC:24525
resolver
uniprot
A0A0C4DGU2
resolver
uniprot
Q5T157
resolver
uniprot
Q9BRQ7
resolver
uniprot_entry
A0A0C4DGU2_HUMAN
resolver
uniprot_entry
MMAC_HUMAN
resolver
uniprot_sec
Q5T157
resolver
uniprot_sec
Q9BRQ7
resolver
amino_acid_sequence
MEPKVAELKQKIEDTLCPFGFEVYPFQVAWYNELLPPAFHLPLPGPTLAFLVLSTPAMFDRALKPFLQSCHLRMLTDPVDQCVAYHLGRVRESLPELQIEIIADYEVHPNRRPKILAQTAAHVAGAAYYYQRQDVEADPWGNQRISGVCIHPRFGGWFAIRGVVLLPGIEVPDLPPRKPHDCVPTRADRIALLEGFNFHWRDWTYRDAVTPQERYSEEQKAYFSTPPAQRLALLGLAQPSEKPSSPSPDLPFTTPAPKKPGNPSRARSWLSPRVSPPASPGP
uniprot
proteins
disease_involvement
DISEASE: Methylmalonic aciduria and homocystinuria, cblC type (MAHCC) [MIM:277400]: An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood. {ECO:0000269|PubMed:16311595, ECO:0000269|PubMed:19700356, ECO:0000269|PubMed:20219402, ECO:0000269|PubMed:22642810, ECO:0000269|PubMed:25809485}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
1.16.1.6
uniprot
proteins
ec_number
2.5.1.151
uniprot
proteins
function
FUNCTION: 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). {ECO:0000269|PubMed:18779575, ECO:0000269|PubMed:19700356, ECO:0000269|PubMed:19801555, ECO:0000269|PubMed:21071249, ECO:0000269|PubMed:21697092, ECO:0000269|PubMed:22642810, ECO:0000269|PubMed:25809485, ECO:0000269|PubMed:27771510, ECO:0000303|PubMed:19801555, ECO:0000303|PubMed:25535791}.
uniprot
proteins
mass_dalton
31728
uniprot
proteins
mutagenesis
MUTAGEN 122; /note="H->A: Reduced affinity for cyanocobalamin."; /evidence="ECO:0000269|PubMed:19700356"; MUTAGEN 206; /note="R->Q: Impairs protein folding."; /evidence="ECO:0000269|PubMed:22642810"; MUTAGEN 230; /note="R->Q: Reduced activity in dealkylation of methylcobalamin."; /evidence="ECO:0000269|PubMed:22642810
uniprot
proteins
protein_family
MMACHC family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16311595
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18779575
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19700356
uniprot
proteins
pubmed
19801555
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20219402
uniprot
proteins
pubmed
21071249
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21697092
uniprot
proteins
pubmed
22642810
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23270877
uniprot
proteins
pubmed
23415655
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25535791
uniprot
proteins
pubmed
25809485
uniprot
proteins
pubmed
26483544
uniprot
proteins
pubmed
27771510
uniprot
proteins
sequence_length
282
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23270877}.
uniprot
proteins