Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:Q99707 MTR

Class:IdReferenceGeneProduct:59167
_chainChangeLogchain:1-1265 added on Fri February 6 2015
_displayNameUniProt:Q99707 MTR
_timestamp2024-11-03 20:10:46
chainchain:1-1265
checksumB04C26BCBE9A57C2
commentFUNCTION Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:27771510). MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (PubMed:16769880, PubMed:17288554, PubMed:27771510). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:16769880, PubMed:27771510).CATALYTIC ACTIVITY (6S)-5-methyl-5,6,7,8-tetrahydrofolate + L-homocysteine = (6S)-5,6,7,8-tetrahydrofolate + L-methionineCOFACTOR Binds 1 zinc ion per subunit.PATHWAY Amino-acid biosynthesis; L-methionine biosynthesis via de novo pathway; L-methionine from L-homocysteine (MetH route): step 1/1.SUBUNIT Monomer (PubMed:17288554). Dimer (PubMed:17288554). Forms a multiprotein complex with MMACHC, MMADHC and MTRR (PubMed:16769880, PubMed:17288554, PubMed:27771510).INTERACTION Widely expressed. Expressed at the highest levels in pancreas, heart, brain, skeletal muscle and placenta (PubMed:8968735, PubMed:8968737). Expressed at lower levels in lung, liver and kidney (PubMed:8968735, PubMed:8968737).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).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the vitamin-B12 dependent methionine synthase family.ONLINE INFORMATION 5-methyltetrahydrofolate-homocysteine methyltransferase entry
descriptionrecommendedName: fullName evidence="21"Methionine synthase shortName: MS ecNumber evidence="11 12"2.1.1.13 alternativeName: 5-methyltetrahydrofolate--homocysteine methyltransferase alternativeName: Cobalamin-dependent methionine synthase alternativeName: Vitamin-B12 dependent methionine synthase
geneNameMTR
identifierQ99707
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Amino-acid biosynthesis
Cobalamin
Cobalt
Cytoplasm
Disease variant
Metal-binding
Methionine biosynthesis
Methyltransferase
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
S-adenosyl-L-methionine
Transferase
Zinc
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
nameMTR
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8962323] ENSEMBL:ENSG00000116984 MTR [Homo sapiens]
secondaryIdentifierMETH_HUMAN
A1L4N8
A9Z1W4
B7ZLW7
B9EGF7
Q99713
Q99723
sequenceLength1265
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8968866] UniProt:Q99707-1 MTR [Homo sapiens]
[ReferenceIsoform:8968867] UniProt:Q99707-2 MTR [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:174376] MTR [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321914] MTR H920D [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321920] MTR E1204* [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321921] MTR A410P [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321933] MTR R585* [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321942] MTR Ile881 [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321944] MTR P1173L [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:3321966] MTR L705Qfs*4 [cytosol] [Homo sapiens]
(referenceSequence)[ReplacedResidue:3321905] L-proline 1173 replaced with L-leucine
[ReplacedResidue:3321907] L-leucine 1141 replaced with L-alanine
[ReplacedResidue:3321909] L-aspartic acid 1131 replaced with glycine
[ReplacedResidue:3321912] L-glutamic acid 1135 replaced with L-arginine
[ReplacedResidue:3321913] L-asparagine 706 replaced with L-tyrosine
[ReplacedResidue:3321916] L-isoleucine 707 replaced with L-asparagine
[ReplacedResidue:3321917] L-leucine 1133 replaced with L-alanine
[ReplacedResidue:3321924] L-leucine 705 replaced with L-glutamine
[ReplacedResidue:3321929] L-histidine 1142 replaced with L-proline
[ReplacedResidue:3321931] L-histidine 920 replaced with L-aspartic acid
List all 22 refering instances
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:Q99707 MTR (59167)