Q8C1A3 · MTRR_MOUSE
- ProteinMethionine synthase reductase
- GeneMtrr
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids696 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin. Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to the inactive cob(II)alamin species. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (By similarity).
Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (PubMed:24074862).
Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme. Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (By similarity).
Also necessary for the utilization of methyl groups from the folate cycle, thereby affecting transgenerational epigenetic inheritance (PubMed:24074862).
Also acts as a molecular chaperone for methionine synthase by stabilizing apoMTR and incorporating methylcob(III)alamin into apoMTR to form the holoenzyme. Also serves as an aquacob(III)alamin reductase by reducing aquacob(III)alamin to cob(II)alamin; this reduction leads to stimulation of the conversion of apoMTR and aquacob(III)alamin to MTR holoenzyme (By similarity).
Miscellaneous
It is debated whether the reduction of free aquacob(II)alamin occurs spontaneously or is enzyme catalyzed.
Catalytic activity
- H+ + 2 methylcob(III)alamin-[methionine synthase] + NADP+ + 2 S-adenosyl-L-homocysteine = 2 cob(II)alamin-[methionine synthase] + NADPH + 2 S-adenosyl-L-methionine
CHEBI:15378 + 2 RHEA-COMP:14714 + CHEBI:58349 + 2 CHEBI:57856 = 2 RHEA-COMP:14715 + CHEBI:57783 + 2 CHEBI:59789 - A + 2 cob(II)alamin + 2 H+ + 2 H2O = AH2 + 2 aquacob(III)alaminThis reaction proceeds in the backward direction.
Cofactor
Protein has several cofactor binding sites:
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 10-14 | FMN (UniProtKB | ChEBI) | ||||
Sequence: TQRGQ | ||||||
Binding site | 93-124 | FMN (UniProtKB | ChEBI) | ||||
Sequence: LLGLGDSEYTYFCNGGKVIDKRLQELGAQRFY | ||||||
Binding site | 289 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 449-452 | FAD (UniProtKB | ChEBI) | ||||
Sequence: RPYS | ||||||
Binding site | 485-488 | FAD (UniProtKB | ChEBI) | ||||
Sequence: GVCT | ||||||
Binding site | 608-609 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: SR | ||||||
Binding site | 622-624 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: YVQ | ||||||
Binding site | 657 | NADP+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 695 | FAD (UniProtKB | ChEBI) | ||||
Sequence: W |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Molecular Function | [methionine synthase] reductase activity | |
Molecular Function | flavin adenine dinucleotide binding | |
Molecular Function | FMN binding | |
Molecular Function | oxidoreductase activity, acting on metal ions, NAD or NADP as acceptor | |
Biological Process | cobalamin metabolic process | |
Biological Process | folic acid metabolic process | |
Biological Process | homocysteine metabolic process | |
Biological Process | methionine biosynthetic process | |
Biological Process | protein stabilization | |
Biological Process | S-adenosylmethionine cycle |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMethionine synthase reductase
- EC number
- Short namesMSR
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8C1A3
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Female mice have more resorptions and more delayed embryos per litter as well as embryonic delays and defects: placentae of mothers are smaller and their embryos are smaller and display myocardial hypoplasia and a higher incidence of ventricular septal defects per litter (PubMed:18413293).
Epigenetic transmission of developmental disorders between generations: a hypomorphic mutation disrupts folate metabolism and is associated with effects on offspring development that are transmitted transgenerationally. The epigenetic influences caused by Mtrr hypomorphic deficiency in mice leads to 2 distinctive phenotypes: 1 an atypical uterine environment in their wild-type daughters that causes growth defects in their wild-type grandprogeny and 2 congenital malformations in their wild-type grandprogeny due to epigenetic inheritance via the germline, the effects of which persist for at least up to 4 wild-type generations after an Mtrr-deficient maternal ancestor. These effects are associated with altered DNA methylation patterns (PubMed:24074862).
Epigenetic transmission of developmental disorders between generations: a hypomorphic mutation disrupts folate metabolism and is associated with effects on offspring development that are transmitted transgenerationally. The epigenetic influences caused by Mtrr hypomorphic deficiency in mice leads to 2 distinctive phenotypes: 1 an atypical uterine environment in their wild-type daughters that causes growth defects in their wild-type grandprogeny and 2 congenital malformations in their wild-type grandprogeny due to epigenetic inheritance via the germline, the effects of which persist for at least up to 4 wild-type generations after an Mtrr-deficient maternal ancestor. These effects are associated with altered DNA methylation patterns (PubMed:24074862).
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000409308 | 1-696 | Methionine synthase reductase | |||
Sequence: MRRFLLLYATQRGQAKAIAEEISEQAVSHGFSADLHCISESEKYDLKTETGPLVMVVSTTGTGDPPDTARKFVKEIHNKTLPTDYFAHLRYGLLGLGDSEYTYFCNGGKVIDKRLQELGAQRFYDTGHADDCVGLELVVEPWIDGLWAALTKHFKSLGGQENMSDTLSRASDAPLSTAMKPELLHIQSQVELLRLEDVGERDSELREQNETNRGQQGRIEDFDSSLVHSVPPLSQSSLSIPAVPPEYLEVHLQESLGQEENQASVPSGDPSFQVPISKAIRLTTNDAVKSTLLLELDISKIEFSHQPGDSFNVTCPNSDREVEELLQRLQLADKRAHRVILKIKTDTKKKGAALPAHVPEGRSLQFILTWCLEIRAVPKKAFLRALAEHTSSATEKRRLQELCSKQGAADYNRFIRDASVCLLDLLLTFPSCQPPLSLLLEHLPKLQPRPYSCASSSLRHPDKLHFVFNIVEFPPSTTAASPRKGVCTGWLATLVAPFLQPNTDVSNADSGDTLAPEIRISPRATNAFHLPEDPSAPIIMVGPGTGVAPFVGFLQHREKLQEQHPDGKFGAMWLFFGCRHKDRDYLFREELRHFLKTGVLTHLKVSFSRDAAPDGEEAPAKYVQDNLQRHSQQVARTLLQENGYIYVCGDAKNMAKDVNDTLIGIISNEAGVDKLEAMKTLATLKQEKRYLQDIWS | ||||||
Modified residue | 171 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 188 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 4-147 | Flavodoxin-like | ||||
Sequence: FLLLYATQRGQAKAIAEEISEQAVSHGFSADLHCISESEKYDLKTETGPLVMVVSTTGTGDPPDTARKFVKEIHNKTLPTDYFAHLRYGLLGLGDSEYTYFCNGGKVIDKRLQELGAQRFYDTGHADDCVGLELVVEPWIDGLW | ||||||
Region | 166-245 | Hinge | ||||
Sequence: TLSRASDAPLSTAMKPELLHIQSQVELLRLEDVGERDSELREQNETNRGQQGRIEDFDSSLVHSVPPLSQSSLSIPAVPP | ||||||
Domain | 269-531 | FAD-binding FR-type | ||||
Sequence: DPSFQVPISKAIRLTTNDAVKSTLLLELDISKIEFSHQPGDSFNVTCPNSDREVEELLQRLQLADKRAHRVILKIKTDTKKKGAALPAHVPEGRSLQFILTWCLEIRAVPKKAFLRALAEHTSSATEKRRLQELCSKQGAADYNRFIRDASVCLLDLLLTFPSCQPPLSLLLEHLPKLQPRPYSCASSSLRHPDKLHFVFNIVEFPPSTTAASPRKGVCTGWLATLVAPFLQPNTDVSNADSGDTLAPEIRISPRATNAFHLP |
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length696
- Mass (Da)77,518
- Last updated2011-05-31 v2
- Checksum740E3A5D9440FC81
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A1Y7VLV0 | A0A1Y7VLV0_MOUSE | Mtrr | 190 | ||
A0A1Y7VM78 | A0A1Y7VM78_MOUSE | Mtrr | 93 | ||
A0A1Y7VKC5 | A0A1Y7VKC5_MOUSE | Mtrr | 157 | ||
A0A1Y7VKD9 | A0A1Y7VKD9_MOUSE | Mtrr | 58 | ||
A0A1Y7VJV6 | A0A1Y7VJV6_MOUSE | Mtrr | 68 | ||
A0A0R4J0G9 | A0A0R4J0G9_MOUSE | Mtrr | 696 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 90 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: R → Q | ||||||
Sequence conflict | 190 | in Ref. 3; AAH25942 | ||||
Sequence: V → F | ||||||
Sequence conflict | 198 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: V → M | ||||||
Sequence conflict | 482 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: P → L | ||||||
Sequence conflict | 508 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: A → V | ||||||
Sequence conflict | 513 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: T → A | ||||||
Sequence conflict | 645 | in Ref. 1; BAC26039/BAE37348 | ||||
Sequence: I → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK028628 EMBL· GenBank· DDBJ | BAC26039.1 EMBL· GenBank· DDBJ | mRNA | ||
AK155359 EMBL· GenBank· DDBJ | BAE33215.1 EMBL· GenBank· DDBJ | mRNA | ||
AK163449 EMBL· GenBank· DDBJ | BAE37348.1 EMBL· GenBank· DDBJ | mRNA | ||
CH466563 EMBL· GenBank· DDBJ | EDL37004.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC025942 EMBL· GenBank· DDBJ | AAH25942.1 EMBL· GenBank· DDBJ | mRNA |