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Q8C1A3

- MTRR_MOUSE

UniProt

Q8C1A3 - MTRR_MOUSE

Protein

Methionine synthase reductase

Gene

Mtrr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 97 (01 Oct 2014)
      Sequence version 2 (31 May 2011)
      Previous versions | rss
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    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

    FAD.By similarity
    FMN.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei289 – 2891NADPBy similarity
    Binding sitei657 – 6571NADPBy similarity
    Binding sitei695 – 6951FADBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi10 – 145FMNPROSITE-ProRule annotation
    Nucleotide bindingi93 – 12432FMNPROSITE-ProRule annotationAdd
    BLAST
    Nucleotide bindingi449 – 4524FADBy similarity
    Nucleotide bindingi485 – 4884FADBy similarity
    Nucleotide bindingi608 – 6092NADPBy similarity
    Nucleotide bindingi622 – 6243NADPBy similarity

    GO - Molecular functioni

    1. [methionine synthase] reductase activity Source: RefGenome
    2. flavin adenine dinucleotide binding Source: UniProtKB
    3. FMN binding Source: InterPro
    4. iron ion binding Source: InterPro
    5. oxidoreductase activity Source: RefGenome
    6. 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 Source: RefGenome
    7. oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor Source: UniProtKB

    GO - Biological processi

    1. DNA methylation Source: UniProtKB
    2. folic acid metabolic process Source: UniProtKB
    3. methionine biosynthetic process Source: UniProtKB-KW

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Methionine biosynthesis

    Keywords - Ligandi

    FAD, Flavoprotein, FMN, NADP, S-adenosyl-L-methionine

    Enzyme and pathway databases

    ReactomeiREACT_189091. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
    REACT_189092. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
    REACT_189118. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_202492. Sulfur amino acid metabolism.

    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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 13

    Organism-specific databases

    MGIiMGI:1891037. Mtrr.

    Subcellular locationi

    Cytoplasm By similarity

    GO - Cellular componenti

    1. cytosol Source: RefGenome
    2. intermediate filament cytoskeleton Source: Ensembl
    3. nucleus Source: Ensembl

    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)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 696696Methionine synthase reductasePRO_0000409308Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei171 – 1711PhosphoserineBy similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PRIDEiQ8C1A3.

    Expressioni

    Gene expression databases

    BgeeiQ8C1A3.
    GenevestigatoriQ8C1A3.

    Interactioni

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000039810.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8C1A3.
    SMRiQ8C1A3. Positions 2-696.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 147144Flavodoxin-likePROSITE-ProRule annotationAdd
    BLAST
    Domaini269 – 531263FAD-binding FR-typePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni166 – 24580HingeBy similarityAdd
    BLAST

    Sequence similaritiesi

    Contains 1 FAD-binding FR-type domain.PROSITE-ProRule annotation
    Contains 1 flavodoxin-like domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0369.
    GeneTreeiENSGT00620000087711.
    HOGENOMiHOG000007485.
    HOVERGENiHBG108376.
    InParanoidiQ8C1A3.
    KOiK00597.
    OrthoDBiEOG7NCV31.
    TreeFamiTF105716.

    Family and domain databases

    Gene3Di1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProiIPR003097. 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]
    PfamiPF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view]
    PRINTSiPR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMiSSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEiPS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q8C1A3-1 [UniParc]FASTAAdd to Basket

    « Hide

    MRRFLLLYAT QRGQAKAIAE EISEQAVSHG FSADLHCISE SEKYDLKTET    50
    GPLVMVVSTT GTGDPPDTAR KFVKEIHNKT LPTDYFAHLR YGLLGLGDSE 100
    YTYFCNGGKV IDKRLQELGA QRFYDTGHAD DCVGLELVVE PWIDGLWAAL 150
    TKHFKSLGGQ ENMSDTLSRA SDAPLSTAMK PELLHIQSQV ELLRLEDVGE 200
    RDSELREQNE TNRGQQGRIE DFDSSLVHSV PPLSQSSLSI PAVPPEYLEV 250
    HLQESLGQEE NQASVPSGDP SFQVPISKAI RLTTNDAVKS TLLLELDISK 300
    IEFSHQPGDS FNVTCPNSDR EVEELLQRLQ LADKRAHRVI LKIKTDTKKK 350
    GAALPAHVPE GRSLQFILTW CLEIRAVPKK AFLRALAEHT SSATEKRRLQ 400
    ELCSKQGAAD YNRFIRDASV CLLDLLLTFP SCQPPLSLLL EHLPKLQPRP 450
    YSCASSSLRH PDKLHFVFNI VEFPPSTTAA SPRKGVCTGW LATLVAPFLQ 500
    PNTDVSNADS GDTLAPEIRI SPRATNAFHL PEDPSAPIIM VGPGTGVAPF 550
    VGFLQHREKL QEQHPDGKFG AMWLFFGCRH KDRDYLFREE LRHFLKTGVL 600
    THLKVSFSRD AAPDGEEAPA KYVQDNLQRH SQQVARTLLQ ENGYIYVCGD 650
    AKNMAKDVND TLIGIISNEA GVDKLEAMKT LATLKQEKRY LQDIWS 696
    Length:696
    Mass (Da):77,518
    Last modified:May 31, 2011 - v2
    Checksum:i740E3A5D9440FC81
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti90 – 901R → Q in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti90 – 901R → Q in BAE37348. (PubMed:16141072)Curated
    Sequence conflicti190 – 1901V → F in AAH25942. (PubMed:15489334)Curated
    Sequence conflicti198 – 1981V → M in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti198 – 1981V → M in BAE37348. (PubMed:16141072)Curated
    Sequence conflicti482 – 4821P → L in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti482 – 4821P → L in BAE37348. (PubMed:16141072)Curated
    Sequence conflicti508 – 5081A → V in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti508 – 5081A → V in BAE37348. (PubMed:16141072)Curated
    Sequence conflicti513 – 5131T → A in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti513 – 5131T → A in BAE37348. (PubMed:16141072)Curated
    Sequence conflicti645 – 6451I → V in BAC26039. (PubMed:16141072)Curated
    Sequence conflicti645 – 6451I → V in BAE37348. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_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.
    UniGeneiMm.205514.

    Genome annotation databases

    EnsembliENSMUST00000045827; ENSMUSP00000039810; ENSMUSG00000034617.
    GeneIDi210009.
    KEGGimmu:210009.
    UCSCiuc007rby.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS26620.1.
    RefSeqi NP_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.
    UniGenei Mm.205514.

    3D structure databases

    ProteinModelPortali Q8C1A3.
    SMRi Q8C1A3. Positions 2-696.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000039810.

    Proteomic databases

    PRIDEi Q8C1A3.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000045827 ; ENSMUSP00000039810 ; ENSMUSG00000034617 .
    GeneIDi 210009.
    KEGGi mmu:210009.
    UCSCi uc007rby.1. mouse.

    Organism-specific databases

    CTDi 4552.
    MGIi MGI:1891037. Mtrr.

    Phylogenomic databases

    eggNOGi COG0369.
    GeneTreei ENSGT00620000087711.
    HOGENOMi HOG000007485.
    HOVERGENi HBG108376.
    InParanoidi Q8C1A3.
    KOi K00597.
    OrthoDBi EOG7NCV31.
    TreeFami TF105716.

    Enzyme and pathway databases

    Reactomei REACT_189091. Defective MTRR causes methylmalonic aciduria and homocystinuria type cblE.
    REACT_189092. Defective MTR causes methylmalonic aciduria and homocystinuria type cblG.
    REACT_189118. Cobalamin (Cbl, vitamin B12) transport and metabolism.
    REACT_202492. Sulfur amino acid metabolism.

    Miscellaneous databases

    NextBioi 372826.
    PROi Q8C1A3.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8C1A3.
    Genevestigatori Q8C1A3.

    Family and domain databases

    Gene3Di 1.20.990.10. 1 hit.
    3.40.50.360. 1 hit.
    InterProi IPR003097. 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 ]
    Pfami PF00667. FAD_binding_1. 1 hit.
    PF00258. Flavodoxin_1. 1 hit.
    PF00175. NAD_binding_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00369. FLAVODOXIN.
    PR00371. FPNCR.
    SUPFAMi SSF52218. SSF52218. 1 hit.
    SSF63380. SSF63380. 1 hit.
    PROSITEi PS51384. FAD_FR. 1 hit.
    PS50902. FLAVODOXIN_LIKE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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.

    Entry informationi

    Entry nameiMTRR_MOUSE
    AccessioniPrimary (citable) accession number: Q8C1A3
    Secondary accession number(s): Q3U2C6, Q8R0Y3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 31, 2011
    Last sequence update: May 31, 2011
    Last modified: October 1, 2014
    This is version 97 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3