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Q8C1A3 (MTRR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 95. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Methionine synthase reductase

Short name=MSR
EC=1.16.1.8
Gene names
Name:Mtrr
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length696 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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. Ref.5

Catalytic activity

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

Cofactor

FAD By similarity.

FMN By similarity.

Subcellular location

Cytoplasm By similarity.

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 (Ref.4). 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 (Ref.5). Ref.4 Ref.5

Sequence similarities

Contains 1 FAD-binding FR-type domain.

Contains 1 flavodoxin-like domain.

Ontologies

Keywords
   Biological processAmino-acid biosynthesis
Methionine biosynthesis
   Cellular componentCytoplasm
   LigandFAD
Flavoprotein
FMN
NADP
S-adenosyl-L-methionine
   Molecular functionOxidoreductase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA methylation

Inferred from mutant phenotype Ref.5. Source: UniProtKB

folic acid metabolic process

Inferred from mutant phenotype Ref.5. Source: UniProtKB

methionine biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

intermediate filament cytoskeleton

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionFMN binding

Inferred from electronic annotation. Source: InterPro

[methionine synthase] reductase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

flavin adenine dinucleotide binding

Inferred from sequence or structural similarity. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

oxidoreductase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen

Inferred from Biological aspect of Ancestor. Source: RefGenome

oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 696696Methionine synthase reductase
PRO_0000409308

Regions

Domain4 – 147144Flavodoxin-like
Domain269 – 531263FAD-binding FR-type
Nucleotide binding10 – 145FMN By similarity
Nucleotide binding93 – 12432FMN By similarity
Nucleotide binding449 – 4524FAD By similarity
Nucleotide binding485 – 4884FAD By similarity
Nucleotide binding608 – 6092NADP By similarity
Nucleotide binding622 – 6243NADP By similarity
Region166 – 24580Hinge By similarity

Sites

Binding site2891NADP By similarity
Binding site6571NADP By similarity
Binding site6951FAD By similarity

Amino acid modifications

Modified residue1711Phosphoserine By similarity

Experimental info

Sequence conflict901R → Q in BAC26039. Ref.1
Sequence conflict901R → Q in BAE37348. Ref.1
Sequence conflict1901V → F in AAH25942. Ref.3
Sequence conflict1981V → M in BAC26039. Ref.1
Sequence conflict1981V → M in BAE37348. Ref.1
Sequence conflict4821P → L in BAC26039. Ref.1
Sequence conflict4821P → L in BAE37348. Ref.1
Sequence conflict5081A → V in BAC26039. Ref.1
Sequence conflict5081A → V in BAE37348. Ref.1
Sequence conflict5131T → A in BAC26039. Ref.1
Sequence conflict5131T → A in BAE37348. Ref.1
Sequence conflict6451I → V in BAC26039. Ref.1
Sequence conflict6451I → V in BAE37348. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q8C1A3 [UniParc].

Last modified May 31, 2011. Version 2.
Checksum: 740E3A5D9440FC81

FASTA69677,518
        10         20         30         40         50         60 
MRRFLLLYAT QRGQAKAIAE EISEQAVSHG FSADLHCISE SEKYDLKTET GPLVMVVSTT 

        70         80         90        100        110        120 
GTGDPPDTAR KFVKEIHNKT LPTDYFAHLR YGLLGLGDSE YTYFCNGGKV IDKRLQELGA 

       130        140        150        160        170        180 
QRFYDTGHAD DCVGLELVVE PWIDGLWAAL TKHFKSLGGQ ENMSDTLSRA SDAPLSTAMK 

       190        200        210        220        230        240 
PELLHIQSQV ELLRLEDVGE RDSELREQNE TNRGQQGRIE DFDSSLVHSV PPLSQSSLSI 

       250        260        270        280        290        300 
PAVPPEYLEV HLQESLGQEE NQASVPSGDP SFQVPISKAI RLTTNDAVKS TLLLELDISK 

       310        320        330        340        350        360 
IEFSHQPGDS FNVTCPNSDR EVEELLQRLQ LADKRAHRVI LKIKTDTKKK GAALPAHVPE 

       370        380        390        400        410        420 
GRSLQFILTW CLEIRAVPKK AFLRALAEHT SSATEKRRLQ ELCSKQGAAD YNRFIRDASV 

       430        440        450        460        470        480 
CLLDLLLTFP SCQPPLSLLL EHLPKLQPRP YSCASSSLRH PDKLHFVFNI VEFPPSTTAA 

       490        500        510        520        530        540 
SPRKGVCTGW LATLVAPFLQ PNTDVSNADS GDTLAPEIRI SPRATNAFHL PEDPSAPIIM 

       550        560        570        580        590        600 
VGPGTGVAPF VGFLQHREKL QEQHPDGKFG AMWLFFGCRH KDRDYLFREE LRHFLKTGVL 

       610        620        630        640        650        660 
THLKVSFSRD AAPDGEEAPA KYVQDNLQRH SQQVARTLLQ ENGYIYVCGD AKNMAKDVND 

       670        680        690 
TLIGIISNEA GVDKLEAMKT LATLKQEKRY LQDIWS 

« Hide

References

« Hide 'large scale' references
[1]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Corpora quadrigemina and Skin.
[2]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: FVB/N.
Tissue: Liver.
[4]"Methionine synthase reductase deficiency results in adverse reproductive outcomes and congenital heart defects in mice."
Deng L., Elmore C.L., Lawrance A.K., Matthews R.G., Rozen R.
Mol. Genet. Metab. 94:336-342(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Mutation in folate metabolism causes epigenetic instability and transgenerational effects on development."
Padmanabhan N., Jia D., Geary-Joo C., Wu X., Ferguson-Smith A.C., Fung E., Bieda M.C., Snyder F.F., Gravel R.A., Cross J.C., Watson E.D.
Cell 155:81-93(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS26620.1.
RefSeqNP_766068.1. NM_172480.2.
XP_006517242.1. XM_006517179.1.
XP_006517243.1. XM_006517180.1.
XP_006517244.1. XM_006517181.1.
XP_006517245.1. XM_006517182.1.
UniGeneMm.205514.

3D structure databases

ProteinModelPortalQ8C1A3.
SMRQ8C1A3. Positions 2-696.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000039810.

Proteomic databases

PRIDEQ8C1A3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045827; ENSMUSP00000039810; ENSMUSG00000034617.
GeneID210009.
KEGGmmu:210009.
UCSCuc007rby.1. mouse.

Organism-specific databases

CTD4552.
MGIMGI:1891037. Mtrr.

Phylogenomic databases

eggNOGCOG0369.
GeneTreeENSGT00620000087711.
HOGENOMHOG000007485.
HOVERGENHBG108376.
InParanoidQ8C1A3.
KOK00597.
OrthoDBEOG7NCV31.
TreeFamTF105716.

Gene expression databases

BgeeQ8C1A3.
GenevestigatorQ8C1A3.

Family and domain databases

Gene3D1.20.990.10. 1 hit.
3.40.50.360. 1 hit.
InterProIPR003097. FAD-binding_1.
IPR017927. Fd_Rdtase_FAD-bd.
IPR001094. Flavdoxin.
IPR008254. Flavodoxin/NO_synth.
IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase.
IPR029039. Flavoprotein-like.
IPR023173. NADPH_Cyt_P450_Rdtase_dom3.
IPR001433. OxRdtase_FAD/NAD-bd.
IPR017938. Riboflavin_synthase-like_b-brl.
[Graphical view]
PfamPF00667. FAD_binding_1. 1 hit.
PF00258. Flavodoxin_1. 1 hit.
PF00175. NAD_binding_1. 1 hit.
[Graphical view]
PRINTSPR00369. FLAVODOXIN.
PR00371. FPNCR.
SUPFAMSSF52218. SSF52218. 1 hit.
SSF63380. SSF63380. 1 hit.
PROSITEPS51384. FAD_FR. 1 hit.
PS50902. FLAVODOXIN_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio372826.
PROQ8C1A3.
SOURCESearch...

Entry information

Entry nameMTRR_MOUSE
AccessionPrimary (citable) accession number: Q8C1A3
Secondary accession number(s): Q3U2C6, Q8R0Y3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 31, 2011
Last sequence update: May 31, 2011
Last modified: July 9, 2014
This is version 95 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot