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Q8C1A3

- MTRR_MOUSE

UniProt

Q8C1A3 - MTRR_MOUSE

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Protein

Methionine synthase reductase

Gene

Mtrr

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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)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
Complete GO annotation...

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.
REACT_241023. Methylation.

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
Complete GO annotation...

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

MaxQBiQ8C1A3.
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

        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)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:
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_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:
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 .
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

MaxQBi Q8C1A3.
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.
REACT_241023. Methylation.

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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 99 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