1. 7,8-Dihydro-L-folic acid
2. 7,8-dihydrofolate
3. 7,8-Dihydrofolic acid
4. 7,8-Dihydropteroylglutamate
5. dihydrofolate
6. H2PteGlu
7. H2PteGlu1
8. L-N-[p-[[(2-amino-7,8-dihydro-4-hydroxy-6-pteridinyl)methyl]amino]benzoyl]-Glutamic acid
9. N-(4-(((2-amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-Glutamic acid
10. N-(4-{[(2-amino-4-oxo-3,4,7,8-tetrahydropteridin-6-yl)methyl]amino}benzoyl)-L-glutamic acid
11. N-(7,8-dihydropteroyl)-L-glutamic acid
12. N-[4-[[(2-amino-1,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid
13. N-[4-[[(2-amino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-Glutamic acid

• Show PDF/HTML

• Cytoplasm (Predicted from LogP)
• Extracellular
• lysosome
• mitochondria

• Blood

1. Navarro-Peran E, Cabezas-Herrera J, Garcia-Canovas F, Durrant MC, Thorneley RN, Rodriguez-Lopez JN: The antifolate activity of tea catechins. Cancer Res. 2005 Mar 15;65(6):2059-64. [PubMed ]
2. Wikipedia

1. Thymidylate synthase
2. Dihydrofolate reductase
3. Folylpolyglutamate synthase, mitochondrial
4. Folylpolyglutamate synthase
5. Dihydrofolate reductase

1. TS
2. TSase

MPVAGSELPRRPLPPAAQERDAEPRPPHGELQYLGQIQHILRCGVRKDDRTGTGTLSVFG
MQARYSLRDEFPLLTTKRVFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDS
LGFSTREEGDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRIIMC
AWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIASYALLTYMIAHI
TGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPKLRILRKVEKIDDFKAEDFQIEG
YNPHPTIKMEMAV

• One Carbon Pool By Folate (map00670 )
• Pyrimidine Metabolism (map00240 )

• 5,10-methylenetetrahydrofolate + dUMP = dihydrofolate + dTMP [RN:R02101]

• Thymidylat_synt (PF00303 )

• None

• None

ATGCCTGTGGCCGGCTCGGAGCTGCCGCGCCGGCCCTTGCCCCCCGCCGCACAGGAGCGG
GACGCCGAGCCGCGTCCGCCGCACGGGGAGCTGCAGTACCTGGGGCAGATCCAACACATC
CTCCGCTGCGGCGTCAGGAAGGACGACCGCACGGGCACCGGCACCCTGTCGGTATTCGGC
ATGCAGGCGCGCTACAGCCTGAGAGATGAATTCCCTCTGCTGACAACCAAACGTGTGTTC
TGGAAGGGTGTTTTGGAGGAGTTGCTGTGGTTTATCAAGGGATCCACAAATGCTAAAGAG
CTGTCTTCCAAGGGAGTGAAAATCTGGGATGCCAATGGATCCCGAGACTTTTTGGACAGC
CTGGGATTCTCCACCAGAGAAGAAGGGGACTTGGGCCCAGTTTATGGCTTCCAGTGGAGG
CATTTTGGGGCAGAATACAGAGATATGGAATCAGATTATTCAGGACAGGGAGTTGACCAA
CTGCAAAGAGTGATTGACACCATCAAAACCAACCCTGACGACAGAAGAATCATCATGTGC
GCTTGGAATCCAAGAGATCTTCCTCTGATGGCGCTGCCTCCATGCCATGCCCTCTGCCAG
TTCTATGTGGTGAACAGTGAGCTGTCCTGCCAGCTGTACCAGAGATCGGGAGACATGGGC
CTCGGTGTGCCTTTCAACATCGCCAGCTACGCCCTGCTCACGTACATGATTGCGCACATC
ACGGGCCTGAAGCCAGGTGACTTTATACACACTTTGGGAGATGCACATATTTACCTGAAT
CACATCGAGCCACTGAAAATTCAGCTTCAGCGAGAACCCAGACCTTTCCCAAAGCTCAGG
ATTCTTCGAAAAGTTGAGAAAATTGATGACTTCAAAGCTGAAGACTTTCAGATTGAAGGG
TACAATCCGCATCCAACTATTAAAATGGAAATGGCTGTTTAG

1. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Nucleotide sequence of a functional cDNA for human thymidylate synthase. Nucleic Acids Res. 1985 Mar 25;13(6):2035-43. [PubMed ]
2. Kaneda S, Nalbantoglu J, Takeishi K, Shimizu K, Gotoh O, Seno T, Ayusawa D: Structural and functional analysis of the human thymidylate synthase gene. J Biol Chem. 1990 Nov 25;265(33):20277-84. [PubMed ]
3. 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 ]
4. Takeishi K, Kaneda S, Ayusawa D, Shimizu K, Gotoh O, Seno T: Human thymidylate synthase gene: isolation of phage clones which cover a functionally active gene and structural analysis of the region upstream from the translation initiation codon. J Biochem (Tokyo). 1989 Oct;106(4):575-83. [PubMed ]
5. Shimizu K, Ayusawa D, Takeishi K, Seno T: Purification and NH2-terminal amino acid sequence of human thymidylate synthase in an overproducing transformant of mouse FM3A cells. J Biochem (Tokyo). 1985 Mar;97(3):845-50. [PubMed ]
6. Davisson VJ, Sirawaraporn W, Santi DV: Expression of human thymidylate synthase in Escherichia coli. J Biol Chem. 1989 Jun 5;264(16):9145-8. [PubMed ]
7. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. [PubMed ]
8. Schiffer CA, Clifton IJ, Davisson VJ, Santi DV, Stroud RM: Crystal structure of human thymidylate synthase: a structural mechanism for guiding substrates into the active site. Biochemistry. 1995 Dec 19;34(50):16279-87. [PubMed ]
9. Phan J, Koli S, Minor W, Dunlap RB, Berger SH, Lebioda L: Human thymidylate synthase is in the closed conformation when complexed with dUMP and raltitrexed, an antifolate drug. Biochemistry. 2001 Feb 20;40(7):1897-902. [PubMed ]
10. Phan J, Steadman DJ, Koli S, Ding WC, Minor W, Dunlap RB, Berger SH, Lebioda L: Structure of human thymidylate synthase suggests advantages of chemotherapy with noncompetitive inhibitors. J Biol Chem. 2001 Apr 27;276(17):14170-7. Epub 2001 Jan 24. [PubMed ]

MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFS
IPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSS
VYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKF
EVYEKND

• Folate and Pterine Biosynthesis (map00790 )
• One Carbon Pool By Folate (map00670 )

• 5,6,7,8-tetrahydrofolate + NADP+ = 7,8-dihydrofolate + NADPH + H+ [RN:R00939]

• DHFR_1 (PF00186 )

• None

• None

ATGGTTGGTTCGCTAAACTGCATCGTCGCTGTGTCCCAGAACATGGGCATCGGCAAGAAC
GGGGACCTGCCCTGGCCACCGCTCAGGAATGAATTCAGATATTTCCAGAGAATGACCACA
ACCTCTTCAGTAGAAGGTAAACAGAATCTGGTGATTATGGGTAAGAAGACCTGGTTCTCC
ATTCCTGAGAAGAATCGACCTTTAAAGGGTAGAATTAATTTAGTTCTCAGCAGAGAACTC
AAGGAACCTCCACAAGGAGCTCATTTTCTTTCCAGAAGTCTAGATGATGCCTTAAAACTT
ACTGAACAACCAGAATTAGCAAATAAAGTAGACATGGTCTGGATAGTTGGTGGCAGTTCT
GTTTATAAGGAAGCCATGAATCACCCAGGCCATCTTAAACTATTTGTGACAAGGATCATG
CAAGACTTTGAAAGTGACACGTTTTTTCCAGAAATTGATTTGGAGAAATATAAACTTCTG
CCAGAATACCCAGGTGTTCTCTCTGATGTCCAGGAGGAGAAAGGCATTAAGTACAAATTT
GAAGTATATGAGAAGAATGATTAA

1. Chen MJ, Shimada T, Moulton AD, Cline A, Humphries RK, Maizel J, Nienhuis AW: The functional human dihydrofolate reductase gene. J Biol Chem. 1984 Mar 25;259(6):3933-43. [PubMed ]
2. Masters JN, Attardi G: The nucleotide sequence of the cDNA coding for the human dihydrofolic acid reductase. Gene. 1983 Jan-Feb;21(1-2):59-63. [PubMed ]
3. Yang JK, Masters JN, Attardi G: Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes. J Mol Biol. 1984 Jun 25;176(2):169-87. [PubMed ]
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. [PubMed ]
5. Oefner C, D'Arcy A, Winkler FK: Crystal structure of human dihydrofolate reductase complexed with folate. Eur J Biochem. 1988 Jun 1;174(2):377-85. [PubMed ]
6. Davies JF 2nd, Delcamp TJ, Prendergast NJ, Ashford VA, Freisheim JH, Kraut J: Crystal structures of recombinant human dihydrofolate reductase complexed with folate and 5-deazafolate. Biochemistry. 1990 Oct 9;29(40):9467-79. [PubMed ]
7. Stockman BJ, Nirmala NR, Wagner G, Delcamp TJ, DeYarman MT, Freisheim JH: Sequence-specific 1H and 15N resonance assignments for human dihydrofolate reductase in solution. Biochemistry. 1992 Jan 14;31(1):218-29. [PubMed ]
8. Lewis WS, Cody V, Galitsky N, Luft JR, Pangborn W, Chunduru SK, Spencer HT, Appleman JR, Blakley RL: Methotrexate-resistant variants of human dihydrofolate reductase with substitutions of leucine 22. Kinetics, crystallography, and potential as selectable markers. J Biol Chem. 1995 Mar 10;270(10):5057-64. [PubMed ]
9. Cody V, Galitsky N, Luft JR, Pangborn W, Rosowsky A, Blakley RL: Comparison of two independent crystal structures of human dihydrofolate reductase ternary complexes reduced with nicotinamide adenine dinucleotide phosphate and the very tight-binding inhibitor PT523. Biochemistry. 1997 Nov 11;36(45):13897-903. [PubMed ]
10. Gangjee A, Vidwans AP, Vasudevan A, Queener SF, Kisliuk RL, Cody V, Li R, Galitsky N, Luft JR, Pangborn W: Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents. J Med Chem. 1998 Aug 27;41(18):3426-34. [PubMed ]
11. Klon AE, Heroux A, Ross LJ, Pathak V, Johnson CA, Piper JR, Borhani DW: Atomic structures of human dihydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 a and 1.05 a resolution. J Mol Biol. 2002 Jul 12;320(3):677-93. [PubMed ]
12. Cody V, Galitsky N, Luft JR, Pangborn W, Gangjee A: Analysis of two polymorphic forms of a pyrido[2,3-d]pyrimidine N9-C10 reversed-bridge antifolate binary complex with human dihydrofolate reductase. Acta Crystallogr D Biol Crystallogr. 2003 Apr;59(Pt 4):654-61. Epub 2003 Mar 25. [PubMed ]
13. Cody V, Luft JR, Pangborn W, Gangjee A: Analysis of three crystal structure determinations of a 5-methyl-6-N-methylanilino pyridopyrimidine antifolate complex with human dihydrofolate reductase. Acta Crystallogr D Biol Crystallogr. 2003 Sep;59(Pt 9):1603-9. Epub 2003 Aug 19. [PubMed ]
14. Cody V, Luft JR, Pangborn W, Gangjee A, Queener SF: Structure determination of tetrahydroquinazoline antifolates in complex with human and Pneumocystis carinii dihydrofolate reductase: correlations between enzyme selectivity and stereochemistry. Acta Crystallogr D Biol Crystallogr. 2004 Apr;60(Pt 4):646-55. Epub 2004 Mar 23. [PubMed ]
15. Cody V, Luft JR, Pangborn W: Understanding the role of Leu22 variants in methotrexate resistance: comparison of wild-type and Leu22Arg variant mouse and human dihydrofolate reductase ternary crystal complexes with methotrexate and NADPH. Acta Crystallogr D Biol Crystallogr. 2005 Feb;61(Pt 2):147-55. Epub 2005 Jan 19. [PubMed ]
16. Kovalevskaya NV, Smurnyy YD, Polshakov VI, Birdsall B, Bradbury AF, Frenkiel T, Feeney J: Solution structure of human dihydrofolate reductase in its complex with trimethoprim and NADPH. J Biomol NMR. 2005 Sep;33(1):69-72. [PubMed ]
17. Reynolds RC, Campbell SR, Fairchild RG, Kisliuk RL, Micca PL, Queener SF, Riordan JM, Sedwick WD, Waud WR, Leung AK, Dixon RW, Suling WJ, Borhani DW: Novel boron-containing, nonclassical antifolates: synthesis and preliminary biological and structural evaluation. J Med Chem. 2007 Jul 12;50(14):3283-9. Epub 2007 Jun 15. [PubMed ]
18. Cody V, Pace J, Makin J, Piraino J, Queener SF, Rosowsky A: Correlations of inhibitor kinetics for Pneumocystis jirovecii and human dihydrofolate reductase with structural data for human active site mutant enzyme complexes. Biochemistry. 2009 Mar 3;48(8):1702-11. [PubMed ]
19. Volpato JP, Yachnin BJ, Blanchet J, Guerrero V, Poulin L, Fossati E, Berghuis AM, Pelletier JN: Multiple conformers in active site of human dihydrofolate reductase F31R/Q35E double mutant suggest structural basis for methotrexate resistance. J Biol Chem. 2009 Jul 24;284(30):20079-89. Epub 2009 May 28. [PubMed ]
20. Gangjee A, Li W, Kisliuk RL, Cody V, Pace J, Piraino J, Makin J: Design, synthesis, and X-ray crystal structure of classical and nonclassical 2-amino-4-oxo-5-substituted-6-ethylthieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors and as potential antitumor agents. J Med Chem. 2009 Aug 13;52(15):4892-902. [PubMed ]

1. Folylpoly-gamma-glutamate synthetase
2. FPGS
3. Tetrahydrofolylpolyglutamate synthase
4. Tetrahydrofolate synthase

MSRARSHLRAALFLAAASARGITTQVAARRGLSAWPVPQEPSMEYQDAVRMLNTLQTNAG
YLEQVKRQRGDPQTQLEAMELYLARSGLQVEDLDRLNIIHVTGTKGKGSTCAFTECILRS
YGLKTGFFSSPHLVQVRERIRINGQPISPELFTKYFWRLYHRLEETKDGSCVSMPPYFRF
LTLMAFHVFLQEKVDLAVVEVGIGGAYDCTNIIRKPVVCGVSSLGIDHTSLLGDTVEKIA
WQKGGIFKQGVPAFTVLQPEGPLAVLRDRAQQISCPLYLCPMLEALEEGGPPLTLGLEGE
HQRSNAALALQLAHCWLQRQDRHGAGEPKASRPGLLWQLPLAPVFQPTSHMRLGLRNTEW
PGRTQVLRRGPLTWYLDGAHTASSAQACVRWFRQALQGRERPSGGPEVRVLLFNATGDRD
PAALLKLLQPCQFDYAVFCPNLTEVSSTGNADQQNFTVTLDQVLLRCLEHQQHWNHLDEE
QASPDLWSAPSPEPGGSASLLLAPHPPHTCSASSLVFSCISHALQWISQGRDPIFQPPSP
PKGLLTHPVAHSGASILREAAAIHVLVTGSLHLVGGVLKLLEPALSQ

• Folate and Pterine Biosynthesis (map00790 )

• ATP + tetrahydropteroyl-[gamma-Glu]n + L-glutamate = ADP + phosphate + tetrahydropteroyl-[gamma-Glu]n+1 [RN:R04241]

• None

• None

ATGTCGCGGGCGCGGAGCCACCTGCGCGCCGCTCTATTCCTGGCAGCGGCGTCTGCGCGC
GGCGTAACGACCCAGGTCGCGGCGCGGCGGGGCTTGAGCGCGTGGCCGGTGCCGCAGGAG
CCGAGCATGGAGTACCAGGATGCCGTGCGCATGCTCAATACCCTGCAGACCAATGCCGGC
TACCTGGAGCAGGTGAAGCGCCAGCGGGGTGACCCTCAGACACAGTTGGAAGCCATGGAA
CTGTACCTGGCACGGAGTGGGCTGCAGGTGGAGGACTTGGACCGGCTGAACATCATCCAC
GTCACTGGGACGAAGGGGAAGGGCTCCACCTGTGCCTTCACGGAATGTATCCTCCGAAGC
TATGGCCTGAAGACGGGATTCTTTAGCTCTCCCCACCTGGTGCAGGTTCGGGAGCGGATC
CGCATCAATGGGCAGCCCATCAGTCCTGAGCTCTTCACCAAGTACTTCTGGCGCCTCTAC
CACCGGCTGGAGGAGACCAAGGATGGCAGCTGTGTCTCCATGCCCCCCTACTTCCGCTTC
CTGACACTCATGGCCTTCCACGTCTTCCTCCAAGAGAAGGTGGACCTGGCAGTGGTGGAG
GTGGGCATTGGCGGGGCTTATGACTGCACCAACATCATCAGGAAGCCTGTGGTGTGCGGA
GTCTCCTCTCTTGGCATCGACCACACCAGCCTCCTGGGGGATACGGTGGAGAAGATCGCA
TGGCAGAAAGGGGGCATCTTTAAGCAAGGTGTCCCTGCCTTCACTGTGCTCCAACCTGAA
GGTCCCCTGGCAGTGCTGAGGGACCGAGCCCAGCAGATCTCATGTCCTCTATACCTGTGT
CCGATGCTGGAGGCCCTCGAGGAAGGGGGGCCGCCGCTGACCCTGGGCCTGGAGGGGGAG
CACCAGCGGTCCAACGCCGCCTTGGCCTTGCAGCTGGCCCACTGCTGGCTGCAGCGGCAG
GACCGCCATGGTGCTGGGGAGCCAAAGGCATCCAGGCCAGGGCTCCTGTGGCAGCTGCCC
CTGGCACCTGTGTTCCAGCCCACATCCCACATGCGGCTCGGGCTTCGGAACACGGAGTGG
CCGGGCCGGACGCAGGTGCTGCGGCGCGGGCCCCTCACCTGGTACCTGGACGGTGCGCAC
ACCGCCAGCAGCGCGCAGGCCTGCGTGCGCTGGTTCCGCCAGGCGCTGCAGGGCCGCGAG
AGGCCGAGCGGTGGCCCCGAGGTTCGAGTCTTGCTCTTCAATGCTACCGGGGACCGGGAC
CCGGCGGCCCTGCTGAAGCTGCTGCAGCCCTGCCAGTTTGACTATGCCGTCTTCTGCCCT
AACCTGACAGAGGTGTCATCCACAGGCAACGCAGACCAACAGAACTTCACAGTGACACTG
GACCAGGTCCTGCTCCGCTGCCTGGAACACCAGCAGCACTGGAACCACCTGGACGAAGAG
CAGGCCAGCCCGGACCTCTGGAGTGTCCCCAGCCCAGAGCCCGGTGGGTCCGCATCCCTG
CTTCTGGCGCCCCACCCACCCCACACCTGCAGTGCCAGCTCCCTCGTCTTCAGCTGCATT
TCACATGCCTTGCAATGGATCAGCCAAGGCCGAGACCCCATCTTCCAGCCACCTAGTCCC
CCAAAGGGCCTCCTCACCCACCCTGTGGCTCACAGTGGGGCCAGCATACTCCGTGAGGCT
GCTGCCATCCATGTGCTAGTCACTGGCAGCCTGCACCTGGTGGGTGGTGTCCTGAAGCTG
CTGGAGCCCGCACTGTCCCAGTAG

1. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. [PubMed ]
2. 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 ]
3. Garrow TA, Admon A, Shane B: Expression cloning of a human cDNA encoding folylpoly(gamma-glutamate) synthetase and determination of its primary structure. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9151-5. [PubMed ]
4. Freemantle SJ, Taylor SM, Krystal G, Moran RG: Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthetase gene. J Biol Chem. 1995 Apr 21;270(16):9579-84. [PubMed ]
5. Taylor SM, Freemantle SJ, Moran RG: Structural organization of the human folypoly-gamma-glutamate synthetase gene: evidence for a single genomic locus. Cancer Res. 1995 Dec 15;55(24):6030-4. [PubMed ]
6. Cichowicz DJ, Shane B: Mammalian folylpoly-gamma-glutamate synthetase. 1. Purification and general properties of the hog liver enzyme. Biochemistry. 1987 Jan 27;26(2):504-12. [PubMed ]

MLNTLQTNAGYLEQVKRQRGDPQTQLEAMELYLARSGLQVEDLDRLNIIHVTGTKGKGST
CAFTECILRSYGLKTGFFSSPHLVQVRERIRINGQPISPELFTKYFWRLYHRLEETKDGS
CVSMPPYFRFLTLMAFHVFLQEKVDLAVVEVGIGGAYDCTNIIRKPVVCGVSSLGIDHTS
LLGDTVEKIAWQKGGIFKQGVPAFTVLQPEGPLAVLRDRAQQISCPLYLCPMLEALEEGG
PPLTLGLEGEHQRSNAALALQLAHCWLQRQDRHGAGEPKASRPGLLWQLPLAPVFQPTSH
MRLGLRNTEWPGRTQVLRRGPLTWYLDGAHTASSAQACVRWFRQALQGRERPSGGPEVRV
LLFNATGDRDPAALLKLLQPCQFDYAVFCPNLTEVSSTGNADQQNFTVTLDQVLLRCLEH
QQHWNHLDEEQASPDLWSAPSPEPGGSASLLLAPHPPHTCSASSLVFSCISHALQWISQG
RDPIFQPPSPPKGLLTHPVAHSGASILREAAAIHVLVTGSLHLVGGVLKLLEPALSQ

• None

• None

ATGCTCAATACCCTGCAGACCAATGCCGGCTACCTGGAGCAGGTGAAGCGCCAGCGGGGT
GACCCTCAGACACAGTTGGAAGCCATGGAACTGTACCTGGCACGGAGTGGGCTGCAGGTG
GAGGACTTGGACCGGCTGAACATCATCCACGTCACTGGGACGAAGGGGAAGGGCTCCACC
TGTGCCTTCACGGAATGTATCCTCCGAAGCTATGGCCTGAAGACGGGATTCTTTAGCTCT
CCCCACCTGGTGCAGGTTCGGGAGCGGATCCGCATCAATGGGCAGCCCATCAGTCCTGAG
CTCTTCACCAAGTACTTCTGGCGCCTCTACCACCGGCTGGAGGAGACCAAGGATGGCAGC
TGTGTCTCCATGCCCCCCTACTTCCGCTTCCTGACACTCATGGCCTTCCACGTCTTCCTC
CAAGAGAAGGTGGACCTGGCAGTGGTGGAGGTGGGCATTGGCGGGGCTTATGACTGCACC
AACATCATCAGGAAGCCTGTGGTGTGCGGAGTCTCCTCTCTTGGCATCGACCACACCAGC
CTCCTGGGGGATACGGTGGAGAAGATCGCATGGCAGAAAGGGGGCATCTTTAAGCAAGGT
GTCCCTGCCTTCACTGTGCTCCAACCTGAAGGTCCCCTGGCAGTGCTGAGGGACCGAGCC
CAGCAGATCTCATGTCCTCTATACCTGTGTCCGATGCTGGAGGCCCTCGAGGAAGGGGGG
CCGCCGCTGACCCTGGGCCTGGAGGGGGAGCACCAGCGGTCCAACGCCGCCTTGGCCTTG
CAGCTGGCCCACTGCTGGCTGCAGCGGCAGGACCGCCATGGTGCTGGGGAGCCAAAGGCA
TCCAGGCCAGGGCTCCTGTGGCAGCTGCCCCTGGCACCTGTGTTCCAGCCCACATCCCAC
ATGCGGCTCGGGCTTCGGAACACGGAGTGGCCGGGCCGGACGCAGGTGCTGCGGCGCGGG
CCCCTCACCTGGTACCTGGACGGTGCGCACACCGCCAGCAGCGCGCAGGCCTGCGTGCGC
TGGTTCCGCCAGGCGCTGCAGGGCCGCGAGAGGCCGAGCGGTGGCCCCGAGGTTCGAGTC
TTGCTCTTCAATGCTACCGGGGACCGGGACCCGGCGGCCCTGCTGAAGCTGCTGCAGCCC
TGCCAGTTTGACTATGCCGTCTTCTGCCCTAACCTGACAGAGGTGTCATCCACAGGCAAC
GCAGACCAACAGAACTTCACAGTGACACTGGACCAGGTCCTGCTCCGCTGCCTGGAACAC
CAGCAGCACTGGAACCACCTGGACGAAGAGCAGGCCAGCCCGGACCTCTGGAGTGCCCCC
AGCCCAGAGCCCGGTGGGTCCGCATCCCTGCTTCTGGCGCCCCACCCACCCCACACCTGC
AGTGCCAGCTCCCTCGTCTTCAGCTGCATTTCACATGCCTTGCAATGGATCAGCCAAGGC
CGAGACCCCATCTTCCAGCCACCTAGTCCCCCAAAGGGCCTCCTCACCCACCCTGTGGCT
CACAGTGGGGCCAGCATACTCCGTGAGGCTGCTGCCATCCATGTGCTAGTCACTGGCAGC
CTGCACCTGGTGGGTGGTGTCCTGAAGCTGCTGGAGCCCGCACTGTCCCAGTAG

1. SubName: cDNA, FLJ93028, Homo sapiens dihydrofolate reductase (DHFR), mRNA

MVGSLNCIVAVSQNMGIGKNGDLPWPPLRNEFRYFQRMTTTSSVEGKQNLVIMGKKTWFS
IPEKNRPLKGRINLVLSRELKEPPQGAHFLSRSLDDALKLTEQPELANKVDMVWIVGGSS
VYKEAMNHPGHLKLFVTRIMQDFESDTFFPEIDLEKYKLLPEYPGVLSDVQEEKGIKYKF
EVYEKND

• DHFR_1 (PF00186 )

• None

• None

ATGGTTGGTTCGCTAAACTGCATCGTCGCTGTGTCCCAGAACATGGGCATCGGCAAGAAC
GGGGACCTGCCCTGGCCACCGCTCAGGAATGAATTCAGATATTTCCAGAGAATGACCACA
ACCTCTTCAGTAGAAGGTAAACAGAATCTGGTGATTATGGGTAAGAAGACCTGGTTCTCC
ATTCCTGAGAAGAATCGACCTTTAAAGGGTAGAATTAATTTAGTTCTCAGCAGAGAACTC
AAGGAACCTCCACAAGGAGCTCATTTTCTTTCCAGAAGTCTAGATGATGCCTTAAAACTT
ACTGAACAACCAGAATTAGCAAATAAAGTAGACATGGTCTGGATAGTTGGTGGCAGTTCT
GTTTATAAGGAAGCCATGAATCACCCAGGCCATCTTAAACTATTTGTGACAAGGATCATG
CAAGACTTTGAAAGTGACACGTTTTTTCCAGAAATTGATTTGGAGAAATATAAACTTCTG
CCAGAATACCCAGGTGTTCTCTCTGATGTCCAGGAGGAGAAAGGCATTAAGTACAAATTT
GAAGTATATGAGAAGAATGATTAA

1. Kao TT, Wang KC, Chang WN, Lin CY, Chen BH, Wu HL, Shi GY, Tsai JN, Fu TF: Characterization and comparative studies of zebrafish and human recombinant dihydrofolate reductases--inhibition by folic acid and polyphenols. Drug Metab Dispos. 2008 Mar;36(3):508-16. Epub 2007 Dec 3. [PubMed ]