Methionine synthase reductase

Details

Name
Methionine synthase reductase
Synonyms
  • 1.16.1.8
  • MSR
Gene Name
MTRR
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037069|Methionine synthase reductase
MGAASVRAGARLVEVALCSFTVTCLEVMRRFLLLYATQQGQAKAIAEEICEQAVVHGFSA
DLHCISESDKYDLKTETAPLVVVVSTTGTGDPPDTARKFVKEIQNQTLPVDFFAHLRYGL
LGLGDSEYTYFCNGGKIIDKRLQELGARHFYDTGHADDCVGLELVVEPWIAGLWPALRKH
FRSSRGQEEISGALPVASPASSRTDLVKSELLHIESQVELLRFDDSGRKDSEVLKQNAVN
SNQSNVVIEDFESSLTRSVPPLSQASLNIPGLPPEYLQVHLQESLGQEESQVSVTSADPV
FQVPISKAVQLTTNDAIKTTLLVELDISNTDFSYQPGDAFSVICPNSDSEVQSLLQRLQL
EDKREHCVLLKIKADTKKKGATLPQHIPAGCSLQFIFTWCLEIRAIPKKAFLRALVDYTS
DSAEKRRLQELCSKQGAADYSRFVRDACACLLDLLLAFPSCQPPLSLLLEHLPKLQPRPY
SCASSSLFHPGKLHFVFNIVEFLSTATTEVLRKGVCTGWLALLVASVLQPNIHASHEDSG
KALAPKISISPRTTNSFHLPDDPSIPIIMVGPGTGIAPFIGFLQHREKLQEQHPDGNFGA
MWLFFGCRHKDRDYLFRKELRHFLKHGILTHLKVSFSRDAPVGEEEAPAKYVQDNIQLHG
QQVARILLQENGHIYVCGDAKNMAKDVHDALVQIISKEVGVEKLEAMKTLATLKEEKRYL
QDIWS
Number of residues
725
Molecular Weight
80409.22
Theoretical pI
6.47
GO Classification
Functions
[methionine synthase] reductase activity / aquacobalamin reductase (NADPH) activity / FAD binding / flavin adenine dinucleotide binding / FMN binding / iron ion binding / NADP binding / NADPH binding / NADPH-hemoprotein reductase activity / 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 / oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor
Processes
cellular nitrogen compound metabolic process / cobalamin metabolic process / DNA methylation / folic acid metabolic process / homocysteine catabolic process / methionine biosynthetic process / methionine metabolic process / methylation / negative regulation of cystathionine beta-synthase activity / oxidation-reduction process / S-adenosylmethionine cycle / small molecule metabolic process / sulfur amino acid metabolic process / vitamin metabolic process / water-soluble vitamin metabolic process / xenobiotic metabolic process
Components
cytoplasm / cytosol / intermediate filament cytoskeleton / nucleoplasm
General Function
Oxidoreductase activity, oxidizing metal ions, nad or nadp as acceptor
Specific 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0016200|Methionine synthase reductase (MTRR)
ATGAGGAGGTTTCTGTTACTATATGCTACACAGCAGGGACAGGCAAAGGCCATCGCAGAA
GAAATATGTGAGCAAGCTGTGGTACATGGATTTTCTGCAGATCTTCACTGTATTAGTGAA
TCCGATAAGTATGACCTAAAAACCGAAACAGCTCCTCTTGTTGTTGTGGTTTCTACCACG
GGCACCGGAGACCCACCCGACACAGCCCGCAAGTTTGTTAAGGAAATACAGAACCAAACA
CTGCCGGTTGATTTCTTTGCTCACCTGCGGTATGGGTTACTGGGTCTCGGTGATTCAGAA
TACACCTACTTTTGCAATGGGGGGAAGATAATTGATAAACGACTTCAAGAGCTTGGAGCC
CGGCATTTCTATGACACTGGACATGCAGATGACTGTGTAGGTTTAGAACTTGTGGTTGAG
CCGTGGATTGCTGGACTCTGGCCAGCCCTCAGAAAGCATTTTAGGTCAAGCAGAGGACAA
GAGGAGATAAGTGGCGCACTCCCGGTGGCATCACCTGCATCCTCGAGGACAGACCTTGTG
AAGTCAGAGCTGCTACACATTGAATCTCAAGTCGAGCTTCTGAGATTCGATGATTCAGGA
AGAAAGGATTCTGAGGTTTTGAAGCAAAATGCAGTGAACAGCAACCAATCCAATGTTGTA
ATTGAAGACTTTGAGTCCTCACTTACCCGTTCGGTACCCCCACTCTCACAAGCCTCTCTG
AATATTCCTGGTTTACCCCCAGAATATTTACAGGTACATCTGCAGGAGTCTCTTGGCCAG
GAGGAAAGCCAAGTATCTGTGACTTCAGCAGATCCAGTTTTTCAAGTGCCAATTTCAAAG
GCAGTTCAACTTACTACGAATGATGCCATAAAAACCACTCTGCTGGTAGAATTGGACATT
TCAAATACAGACTTTTCCTATCAGCCTGGAGATGCCTTCAGCGTGATCTGCCCTAACAGT
GATTCTGAGGTACAAAGCCTACTCCAAAGACTGCAGCTTGAAGATAAAAGAGAGCACTGC
GTCCTTTTGAAAATAAAGGCAGACACAAAGAAGAAAGGAGCTACCTTACCCCAGCATATA
CCTGCGGGATGTTCTCTCCAGTTCATTTTTACCTGGTGTCTTGAAATCCGAGCAATTCCT
AAAAAGGCATTTTTGCGAGCCCTTGTGGACTATACCAGTGACAGTGCTGAAAAGCGCAGG
CTACAGGAGCTGTGCAGTAAACAAGGGGCAGCCGATTATAGCCGCTTTGTACGAGATGCC
TGTGCCTGCTTGTTGGATCTCCTCCTCGCTTTCCCTTCTTGCCAGCCACCACTCAGTCTC
CTGCTCGAACATCTTCCTAAACTTCAACCCAGACCATATTCGTGTGCAAGCTCAAGTTTA
TTTCACCCAGGAAAGCTCCATTTTGTCTTCAACATTGTGGAATTTCTGTCTACTGCCACA
ACAGAGGTTCTGCGGAAGGGAGTATGTACAGGCTGGCTGGCCTTGTTGGTTGCTTCAGTT
CTTCAGCCAAACATACATGCATCCCATGAAGACAGCGGGAAAGCCCTGGCTCCTAAGATA
TCCATCTCTCCTCGAACAACAAATTCTTTCCACTTACCAGATGACCCCTCAATCCCCATC
ATAATGGTGGGTCCAGGAACCGGCATAGCCCCGTTTATTGGGTTCCTACAACATAGAGAG
AAACTCCAAGAACAACACCCAGATGGAAATTTTGGAGCAATGTGGTTGTTTTTTGGCTGC
AGGCATAAGGATAGGGATTATCTATTCAGAAAAGAGCTCAGACATTTCCTTAAGCATGGG
ATCTTAACTCATCTAAAGGTTTCCTTCTCAAGAGATGCTCCTGTTGGGGAGGAGGAAGCC
CCAGCAAAGTATGTGCAAGACAACATCCAGCTTCATGGCCAGCAGGTGGCGAGAATCCTC
CTCCAGGAGAACGGCCATATTTATGTGTGTGGAGATGCAAAGAATATGGCCAAGGATGTA
CATGATGCCCTTGTGCAAATAATAAGCAAAGAGGTTGGAGTTGAAAAACTAGAAGCAATG
AAAACCCTGGCCACTTTAAAAGAAGAAAAACGCTACCTTCAGGATATTTGGTCATAA
Chromosome Location
5
Locus
5p15.3-p15.2
External Identifiers
ResourceLink
UniProtKB IDQ9UBK8
UniProtKB Entry NameMTRR_HUMAN
GenBank Protein ID6572540
GenBank Gene IDAF121213
GenAtlas IDMTRR
HGNC IDHGNC:7473
General References
  1. Leclerc D, Odievre M, Wu Q, Wilson A, Huizenga JJ, Rozen R, Scherer SW, Gravel RA: Molecular cloning, expression and physical mapping of the human methionine synthase reductase gene. Gene. 1999 Nov 15;240(1):75-88. [Article]
  2. Leclerc D, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, Heng HH, Rommens JM, Scherer SW, Rosenblatt DS, Gravel RA: Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3059-64. [Article]
  3. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Froese DS, Wu X, Zhang J, Dumas R, Schoel WM, Amrein M, Gravel RA: Restricted role for methionine synthase reductase defined by subcellular localization. Mol Genet Metab. 2008 May;94(1):68-77. doi: 10.1016/j.ymgme.2007.11.019. Epub 2008 Jan 24. [Article]
  6. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  7. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  8. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  9. Wolthers KR, Lou X, Toogood HS, Leys D, Scrutton NS: Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. Biochemistry. 2007 Oct 23;46(42):11833-44. Epub 2007 Sep 25. [Article]
  10. Wilson A, Leclerc D, Rosenblatt DS, Gravel RA: Molecular basis for methionine synthase reductase deficiency in patients belonging to the cblE complementation group of disorders in folate/cobalamin metabolism. Hum Mol Genet. 1999 Oct;8(11):2009-16. [Article]
  11. Wilson A, Platt R, Wu Q, Leclerc D, Christensen B, Yang H, Gravel RA, Rozen R: A common variant in methionine synthase reductase combined with low cobalamin (vitamin B12) increases risk for spina bifida. Mol Genet Metab. 1999 Aug;67(4):317-23. [Article]
  12. Doolin MT, Barbaux S, McDonnell M, Hoess K, Whitehead AS, Mitchell LE: Maternal genetic effects, exerted by genes involved in homocysteine remethylation, influence the risk of spina bifida. Am J Hum Genet. 2002 Nov;71(5):1222-6. Epub 2002 Oct 9. [Article]
  13. O'Leary VB, Mills JL, Pangilinan F, Kirke PN, Cox C, Conley M, Weiler A, Peng K, Shane B, Scott JM, Parle-McDermott A, Molloy AM, Brody LC: Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association. Mol Genet Metab. 2005 Jul;85(3):220-7. Epub 2005 Mar 17. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00115Cyanocobalaminapproved, nutraceuticalunknowncofactorDetails
DB00134Methionineapproved, nutraceuticalunknownproduct ofDetails