Methionine synthase reductase

NameMethionine synthase reductase
Synonyms1.16.1.8 MSR
Gene NameMTRR
OrganismHuman
Amino acid sequence
>lcl|BSEQ0037069|Methionine synthase reductase
MGAASVRAGARLVEVALCSFTVTCLEVMRRFLLLYATQQGQAKAIAEEICEQAVVHGFSA
DLHCISESDKYDLKTETAPLVVVVSTTGTGDPPDTARKFVKEIQNQTLPVDFFAHLRYGL
LGLGDSEYTYFCNGGKIIDKRLQELGARHFYDTGHADDCVGLELVVEPWIAGLWPALRKH
FRSSRGQEEISGALPVASPASSRTDLVKSELLHIESQVELLRFDDSGRKDSEVLKQNAVN
SNQSNVVIEDFESSLTRSVPPLSQASLNIPGLPPEYLQVHLQESLGQEESQVSVTSADPV
FQVPISKAVQLTTNDAIKTTLLVELDISNTDFSYQPGDAFSVICPNSDSEVQSLLQRLQL
EDKREHCVLLKIKADTKKKGATLPQHIPAGCSLQFIFTWCLEIRAIPKKAFLRALVDYTS
DSAEKRRLQELCSKQGAADYSRFVRDACACLLDLLLAFPSCQPPLSLLLEHLPKLQPRPY
SCASSSLFHPGKLHFVFNIVEFLSTATTEVLRKGVCTGWLALLVASVLQPNIHASHEDSG
KALAPKISISPRTTNSFHLPDDPSIPIIMVGPGTGIAPFIGFLQHREKLQEQHPDGNFGA
MWLFFGCRHKDRDYLFRKELRHFLKHGILTHLKVSFSRDAPVGEEEAPAKYVQDNIQLHG
QQVARILLQENGHIYVCGDAKNMAKDVHDALVQIISKEVGVEKLEAMKTLATLKEEKRYL
QDIWS
Number of residues725
Molecular Weight80409.22
Theoretical pI6.47
GO Classification
Functions
    NADPH-hemoprotein reductase activity
FMN binding
iron ion binding
NADPH binding
NADP binding
flavin adenine dinucleotide binding
FAD binding
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
[methionine synthase] reductase activity
aquacobalamin reductase (NADPH) activity
oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor
Processes
    oxidation-reduction process
vitamin metabolic process
methylation
water-soluble vitamin metabolic process
methionine biosynthetic process
xenobiotic metabolic process
S-adenosylmethionine cycle
sulfur amino acid metabolic process
DNA methylation
cobalamin metabolic process
cellular nitrogen compound metabolic process
homocysteine catabolic process
small molecule metabolic process
folic acid metabolic process
methionine metabolic process
negative regulation of cystathionine beta-synthase activity
Components
    intermediate filament cytoskeleton
cytoplasm
cytosol
nucleoplasm
General FunctionOxidoreductase activity, oxidizing metal ions, nad or nadp as acceptor
Specific FunctionInvolved 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.
Transmembrane Regions
GenBank Protein ID6572540
UniProtKB IDQ9UBK8
UniProtKB Entry NameMTRR_HUMAN
Cellular LocationCytoplasm
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
GenBank Gene IDAF121213
GeneCard IDNone
GenAtlas IDMTRR
HGNC IDHGNC:7473
Chromosome Location5
Locus5p15.3-p15.2
References
  1. 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.[12375236 ]
  2. 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.[15979034 ]
  3. 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.[10564814 ]
  4. 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.[9501215 ]
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  6. 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.[18221906 ]
  7. 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.[20068231 ]
  8. 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.[21269460 ]
  9. 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.[24275569 ]
  10. 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.[17892308 ]
  11. 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.[10484769 ]
  12. 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.[10444342 ]
  13. 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.[15489334 ]

Related FRC

FRCD ID Name Exact Mass Structure




F05341



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149.208




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1346.377




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1356.396