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Identification
HMDB Protein ID HMDBP00421
Secondary Accession Numbers
  • 5658
  • HMDBP09378
Name Methionine synthase reductase
Synonyms
  1. MSR
Gene Name MTRR
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Involved in the reductive regeneration of cob(I)alamin cofactor required for the maintenance of methionine synthase in a functional state.
Pathways Not Available
Reactions
[methionine synthase]-methylcob(I)alamin + S-Adenosylhomocysteine + NADP → [methionine synthase]-cob(II)alamin + NADPH + S-Adenosylmethionine details
GO Classification
Biological Process
methionine biosynthetic process
methionine metabolic process
Cellular Component
cytosol
nucleus
intermediate filament cytoskeleton
Function
ion binding
cation binding
metal ion binding
binding
nucleotide binding
catalytic activity
transition metal ion binding
iron ion binding
fmn binding
oxidoreductase activity
Molecular Function
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NADH or NADPH as one donor, and incorporation of one atom of oxygen
NADP binding
[methionine synthase] reductase activity
iron ion binding
FMN binding
flavin adenine dinucleotide binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Isoform A:Cytoplasm
Gene Properties
Chromosome Location 5
Locus 5p15.31
SNPs MTRR
Gene Sequence
>2178 bp
ATGGGCGCTGCGTCAGTGCGCGCTGGCGCAAGGTTGGTGGAAGTCGCGTTGTGCAGTTTC
ACTGTTACATGCCTTGAAGTGATGAGGAGGTTTCTGTTACTATATGCTACACAGCAGGGA
CAGGCAAAGGCCATCGCAGAAGAAATGTGTGAGCAAGCTGTGGTACATGGATTTTCTGCA
GATCTTCACTGTATTAGTGAATCCGATAAGTATGACCTAAAAACCGAAACAGCTCCTCTT
GTTGTTGTGGTTTCTACCACGGGCACCGGAGACCCACCCGACACAGCCCGCAAGTTTGTT
AAGGAAATACAGAACCAAACACTGCCGGTTGATTTCTTTGCTCACCTGCGGTATGGGTTA
CTGGGTCTCGGTGATTCAGAATACACCTACTTTTGCAATGGGGGGAAGATAATTGATAAA
CGACTTCAAGAGCTTGGAGCCCGGCATTTCTATGACACTGGACATGCAGATGACTGTGTA
GGTTTAGAACTTGTGGTTGAGCCGTGGATTGCTGGACTCTGGCCAGCCCTCAGAAAGCAT
TTTAGGTCAAGCAGAGGACAAGAGGAGATAAGTGGCGCACTCCCGGTGGCATCACCTGCA
TCCTTGAGGACAGACCTTGTGAAGTCAGAGCTGCTACACATTGAATCTCAAGTCGAGCTT
CTGAGATTCGATGATTCAGGAAGAAAGGATTCTGAGGTTTTGAAGCAAAATGCAGTGAAC
AGCAACCAATCCAATGTTGTAATTGAAGACTTTGAGTCCTCACTTACCCGTTCGGTACCC
CCACTCTCACAAGCCTCTCTGAATATTCCTGGTTTACCCCCAGAATATTTACAGGTACAT
CTGCAGGAGTCTCTTGGCCAGGAGGAAAGCCAAGTATCTGTGACTTCAGCAGATCCAGTT
TTTCAAGTGCCAATTTCAAAGGCAGTTCAACTTACTACGAATGATGCCATAAAAACCACT
CTGCTGGTAGAATTGGACATTTCAAATACAGACTTTTCCTATCAGCCTGGAGATGCCTTC
AGCGTGATCTGCCCTAACAGTGATTCTGAGGTACAAAGCCTACTCCAAAGACTGCAGCTT
GAAGATAAAAGAGAGCACTGCGTCCTTTTGAAAATAAAGGCAGACACAAAGAAGAAAGGA
GCTACCTTACCCCAGCATATACCTGCGGGATGTTCTCTCCAGTTCATTTTTACCTGGTGT
CTTGAAATCCGAGCAATTCCTAAAAAGGCATTTTTGCGAGCCCTTGTGGACTATACCAGT
GACAGTGCTGAAAAGCGCAGGCTACAGGAGCTGTGCAGTAAACAAGGGGCAGCCGATTAT
AGCCGCTTTGTACGAGATGCCTGTGCCTGCTTGTTGGATCTCCTCCTCGCTTTCCCTTCT
TGCCAGCCACCACTCAGTCTCCTGCTCGAACATCTTCCTAAACTTCAACCCAGACCATAT
TCGTGTGCAAGCTCAAGTTTATTTCACCCAGGAAAGCTCCATTTTGTCTTCAACATTGTG
GAATTTCTGTCTACTGCCACAACAGAGGTTCTGCGGAAGGGAGTATGTACAGGCTGGCTG
GCCTTGTTGGTTGCTTCAGTTCTTCAGCCAAACATACATGCATCCCATGAAGACAGCGGG
AAAGCCCTGGCTCCTAAGATATCCATCTCTCCTCGAACAACAAATTCTTTCCACTTACCA
GATGACCCCTCAATCCCCATCATAATGGTGGGTCCAGGAACCGGCATAGCCCCGTTTATT
GGGTTCCTACAACATAGAGAGAAACTCCAAGAACAACACCCAGATGGAAATTTTGGAGCA
ATGTGGTTGTTTTTTGGCTGCAGGCATAAGGATAGGGATTATCTATTCAGAAAAGAGCTC
AGACATTTCCTTAAGCATGGGATCTTAACTCATCTAAAGGTTTCCTTCTCAAGAGATGCT
CCTGTTGGGGAGGAGGAAGCCCCAGCAAAGTATGTACAAGACAACATCCAGCTTCATGGC
CAGCAGGTGGCGAGAATCCTCCTCCAGGAGAACGGCCATATTTATGTGTGTGGAGATGCA
AAGAATATGGCCAAGGATGTACATGATGCCCTTGTGCAAATAATAAGCAAAGAGGTTGGA
GTTGAAAAACTAGAAGCAATGAAAACCCTGGCCACTTTAAAAGAAGAAAAACGCTACCTT
CAGGATATTTGGTCATAA
Protein Properties
Number of Residues 725
Molecular Weight 77672.995
Theoretical pI 6.498
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Methionine synthase reductase
MGAASVRAGARLVEVALCSFTVTCLEVMRRFLLLYATQQGQAKAIAEEICEQAVVHGFSA
DLHCISESDKYDLKTETAPLVVVVSTTGTGDPPDTARKFVKEIQNQTLPVDFFAHLRYGL
LGLGDSEYTYFCNGGKIIDKRLQELGARHFYDTGHADDCVGLELVVEPWIAGLWPALRKH
FRSSRGQEEISGALPVASPASSRTDLVKSELLHIESQVELLRFDDSGRKDSEVLKQNAVN
SNQSNVVIEDFESSLTRSVPPLSQASLNIPGLPPEYLQVHLQESLGQEESQVSVTSADPV
FQVPISKAVQLTTNDAIKTTLLVELDISNTDFSYQPGDAFSVICPNSDSEVQSLLQRLQL
EDKREHCVLLKIKADTKKKGATLPQHIPAGCSLQFIFTWCLEIRAIPKKAFLRALVDYTS
DSAEKRRLQELCSKQGAADYSRFVRDACACLLDLLLAFPSCQPPLSLLLEHLPKLQPRPY
SCASSSLFHPGKLHFVFNIVEFLSTATTEVLRKGVCTGWLALLVASVLQPNIHASHEDSG
KALAPKISISPRTTNSFHLPDDPSIPIIMVGPGTGIAPFIGFLQHREKLQEQHPDGNFGA
MWLFFGCRHKDRDYLFRKELRHFLKHGILTHLKVSFSRDAPVGEEEAPAKYVQDNIQLHG
QQVARILLQENGHIYVCGDAKNMAKDVHDALVQIISKEVGVEKLEAMKTLATLKEEKRYL
QDIWS
GenBank ID Protein 6561339
UniProtKB/Swiss-Prot ID Q9UBK8
UniProtKB/Swiss-Prot Entry Name MTRR_HUMAN
PDB IDs
GenBank Gene ID AF121214
GeneCard ID MTRR
GenAtlas ID MTRR
HGNC ID HGNC:7473
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:12375236 ]
  3. 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. [PubMed:15979034 ]
  4. 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. [PubMed:15372022 ]
  5. 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. [PubMed:10564814 ]
  6. 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. [PubMed:9501215 ]
  7. 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. [PubMed:18221906 ]
  8. 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. [PubMed:10484769 ]
  9. 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. [PubMed:10444342 ]