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Protein

Methionine synthase reductase

Gene

Mtrr

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the reductive regeneration of cob(I)alamin (vitamin B12) cofactor required for the maintenance of methionine synthase in a functional state. Necessary for utilization of methylgroups from the folate cycle, thereby affecting transgenerational epigenetic inheritance. Folate pathway donates methyl groups necessary for cellular methylation and affects different pathways such as DNA methylation, possibly explaining the transgenerational epigenetic inheritance effects.1 Publication

Catalytic activityi

2 [methionine synthase]-methylcob(I)alamin + 2 S-adenosylhomocysteine + NADP+ = 2 [methionine synthase]-cob(II)alamin + NADPH + 2 S-adenosyl-L-methionine.

Cofactori

Protein has several cofactor binding sites:
  • FADBy similarity
  • FMNBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei289NADPBy similarity1
Binding sitei657NADPBy similarity1
Binding sitei695FADBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi10 – 14FMNPROSITE-ProRule annotation5
Nucleotide bindingi93 – 124FMNPROSITE-ProRule annotationAdd BLAST32
Nucleotide bindingi449 – 452FADBy similarity4
Nucleotide bindingi485 – 488FADBy similarity4
Nucleotide bindingi608 – 609NADPBy similarity2
Nucleotide bindingi622 – 624NADPBy similarity3

GO - Molecular functioni

GO - Biological processi

  • DNA methylation Source: UniProtKB
  • folic acid metabolic process Source: UniProtKB
  • homocysteine catabolic process Source: MGI
  • homocysteine metabolic process Source: BHF-UCL
  • methionine biosynthetic process Source: BHF-UCL
  • negative regulation of cystathionine beta-synthase activity Source: MGI
  • oxidation-reduction process Source: BHF-UCL
  • protein stabilization Source: MGI
  • S-adenosylmethionine cycle Source: BHF-UCL

Keywordsi

Molecular functionOxidoreductase
Biological processAmino-acid biosynthesis, Methionine biosynthesis
LigandFAD, Flavoprotein, FMN, NADP, S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
Methionine synthase reductase (EC:1.16.1.8)
Short name:
MSR
Gene namesi
Name:Mtrr
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1891037 Mtrr

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Disruption phenotypei

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).2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004093081 – 696Methionine synthase reductaseAdd BLAST696

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei171PhosphoserineBy similarity1
Modified residuei188PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8C1A3
MaxQBiQ8C1A3
PaxDbiQ8C1A3
PeptideAtlasiQ8C1A3
PRIDEiQ8C1A3

PTM databases

iPTMnetiQ8C1A3
PhosphoSitePlusiQ8C1A3

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000039810

Structurei

3D structure databases

ProteinModelPortaliQ8C1A3
SMRiQ8C1A3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 147Flavodoxin-likePROSITE-ProRule annotationAdd BLAST144
Domaini269 – 531FAD-binding FR-typePROSITE-ProRule annotationAdd BLAST263

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni166 – 245HingeBy similarityAdd BLAST80

Phylogenomic databases

eggNOGiKOG1158 Eukaryota
COG0369 LUCA
HOGENOMiHOG000007485
HOVERGENiHBG108376
InParanoidiQ8C1A3
KOiK00597
TreeFamiTF105716

Family and domain databases

Gene3Di1.20.990.102 hits
3.40.50.3601 hit
InterProiView protein in InterPro
IPR003097 FAD-binding_1
IPR017927 Fd_Rdtase_FAD-bd
IPR001094 Flavdoxin-like
IPR008254 Flavodoxin/NO_synth
IPR001709 Flavoprot_Pyr_Nucl_cyt_Rdtase
IPR029039 Flavoprotein-like_sf
IPR023173 NADPH_Cyt_P450_Rdtase_alpha
IPR001433 OxRdtase_FAD/NAD-bd
IPR017938 Riboflavin_synthase-like_b-brl
PfamiView protein in Pfam
PF00667 FAD_binding_1, 1 hit
PF00258 Flavodoxin_1, 1 hit
PF00175 NAD_binding_1, 1 hit
PRINTSiPR00369 FLAVODOXIN
PR00371 FPNCR
SUPFAMiSSF52218 SSF52218, 1 hit
SSF63380 SSF63380, 1 hit
PROSITEiView protein in PROSITE
PS51384 FAD_FR, 1 hit
PS50902 FLAVODOXIN_LIKE, 1 hit

Sequencei

Sequence statusi: Complete.

Q8C1A3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRRFLLLYAT QRGQAKAIAE EISEQAVSHG FSADLHCISE SEKYDLKTET
60 70 80 90 100
GPLVMVVSTT GTGDPPDTAR KFVKEIHNKT LPTDYFAHLR YGLLGLGDSE
110 120 130 140 150
YTYFCNGGKV IDKRLQELGA QRFYDTGHAD DCVGLELVVE PWIDGLWAAL
160 170 180 190 200
TKHFKSLGGQ ENMSDTLSRA SDAPLSTAMK PELLHIQSQV ELLRLEDVGE
210 220 230 240 250
RDSELREQNE TNRGQQGRIE DFDSSLVHSV PPLSQSSLSI PAVPPEYLEV
260 270 280 290 300
HLQESLGQEE NQASVPSGDP SFQVPISKAI RLTTNDAVKS TLLLELDISK
310 320 330 340 350
IEFSHQPGDS FNVTCPNSDR EVEELLQRLQ LADKRAHRVI LKIKTDTKKK
360 370 380 390 400
GAALPAHVPE GRSLQFILTW CLEIRAVPKK AFLRALAEHT SSATEKRRLQ
410 420 430 440 450
ELCSKQGAAD YNRFIRDASV CLLDLLLTFP SCQPPLSLLL EHLPKLQPRP
460 470 480 490 500
YSCASSSLRH PDKLHFVFNI VEFPPSTTAA SPRKGVCTGW LATLVAPFLQ
510 520 530 540 550
PNTDVSNADS GDTLAPEIRI SPRATNAFHL PEDPSAPIIM VGPGTGVAPF
560 570 580 590 600
VGFLQHREKL QEQHPDGKFG AMWLFFGCRH KDRDYLFREE LRHFLKTGVL
610 620 630 640 650
THLKVSFSRD AAPDGEEAPA KYVQDNLQRH SQQVARTLLQ ENGYIYVCGD
660 670 680 690
AKNMAKDVND TLIGIISNEA GVDKLEAMKT LATLKQEKRY LQDIWS
Length:696
Mass (Da):77,518
Last modified:May 31, 2011 - v2
Checksum:i740E3A5D9440FC81
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti90R → Q in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti90R → Q in BAE37348 (PubMed:16141072).Curated1
Sequence conflicti190V → F in AAH25942 (PubMed:15489334).Curated1
Sequence conflicti198V → M in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti198V → M in BAE37348 (PubMed:16141072).Curated1
Sequence conflicti482P → L in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti482P → L in BAE37348 (PubMed:16141072).Curated1
Sequence conflicti508A → V in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti508A → V in BAE37348 (PubMed:16141072).Curated1
Sequence conflicti513T → A in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti513T → A in BAE37348 (PubMed:16141072).Curated1
Sequence conflicti645I → V in BAC26039 (PubMed:16141072).Curated1
Sequence conflicti645I → V in BAE37348 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK028628 mRNA Translation: BAC26039.1
AK155359 mRNA Translation: BAE33215.1
AK163449 mRNA Translation: BAE37348.1
CH466563 Genomic DNA Translation: EDL37004.1
BC025942 mRNA Translation: AAH25942.1
CCDSiCCDS26620.1
RefSeqiNP_001295404.1, NM_001308475.1
NP_766068.1, NM_172480.3
XP_006517242.1, XM_006517179.3
XP_006517244.1, XM_006517181.3
XP_006517245.1, XM_006517182.1
UniGeneiMm.205514

Genome annotation databases

GeneIDi210009
KEGGimmu:210009
UCSCiuc007rby.1 mouse

Similar proteinsi

Entry informationi

Entry nameiMTRR_MOUSE
AccessioniPrimary (citable) accession number: Q8C1A3
Secondary accession number(s): Q3U2C6, Q8R0Y3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 31, 2011
Last sequence update: May 31, 2011
Last modified: February 28, 2018
This is version 126 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome