MGP Database

MGP001976

UniProt Annotations

Entry Information

Gene Name	5-methyltetrahydrofolate-homocysteine methyltransferase
Protein Entry	METH_HUMAN
UniProt ID	Q99707
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q99707-1; Sequence=Displayed; Name=2; IsoId=Q99707-2; Sequence=VSP_057283; Note=No experimental confirmation available.;
Catalytic Activity	5-methyltetrahydrofolate + L-homocysteine = tetrahydrofolate + L-methionine.
Cofactor	Name=methyl(III)cobalamin; Xref=ChEBI:CHEBI:28115;
Cofactor	Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
Disease	Folate-sensitive neural tube defects (FS-NTD) [MIM:601634]: The most common NTDs are open spina bifida (myelomeningocele) and anencephaly. {ECO:0000269\|PubMed:12375236}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease	Homocystinuria-megaloblastic anemia, cblG complementation type (HMAG) [MIM:250940]: An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. {ECO:0000269\|PubMed:8968736, ECO:0000269\|PubMed:8968737}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Domain	Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L- methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L- methionine and flavodoxin regenerates methylcobalamin (By similarity). {ECO:0000250}.
Function	Catalyzes the transfer of a methyl group from methyl- cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity). {ECO:0000250}.
Interaction	Q9Y4U1:MMACHC; NbExp=3; IntAct=EBI-1045782, EBI-9775184;
Miscellaneous	L-homocysteine is bound via the zinc atom. {ECO:0000250}.
Pathway	Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.
Similarity	Belongs to the vitamin-B12 dependent methionine synthase family. {ECO:0000305}.
Similarity	Contains 1 AdoMet activation domain. {ECO:0000255\|PROSITE-ProRule:PRU00346}.
Similarity	Contains 1 B12-binding domain. {ECO:0000255\|PROSITE- ProRule:PRU00666}.
Similarity	Contains 1 B12-binding N-terminal domain. {ECO:0000305}.
Similarity	Contains 1 Hcy-binding domain. {ECO:0000255\|PROSITE- ProRule:PRU00333}.
Similarity	Contains 1 pterin-binding domain. {ECO:0000255\|PROSITE-ProRule:PRU00334}.
Subcellular Location	Cytoplasm.
Tissue Specificity	Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta. Expressed at lower levels in lung, liver and kidney.
Web Resource	Name=Wikipedia; Note=5-methyltetrahydrofolate- homocysteine methyltransferase entry; URL="http://en.wikipedia.org/wiki/5-Methyltetrahydrofolate-homocysteine_methyltransferase";