S-Adenosylhomocysteine (T3D4455)

General Function:

Zinc ion binding

Specific Function:

Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9.

Gene Name:

DNMT1

Uniprot ID:

P26358

Molecular Weight:

183163.635 Da

References

1. Isakovic L, Saavedra OM, Llewellyn DB, Claridge S, Zhan L, Bernstein N, Vaisburg A, Elowe N, Petschner AJ, Rahil J, Beaulieu N, Gauthier F, MacLeod AR, Delorme D, Besterman JM, Wahhab A: Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6. doi: 10.1016/j.bmcl.2009.03.132. Epub 2009 Mar 28. [19364644 ]
2. Baud MG, Leiser T, Haus P, Samlal S, Wong AC, Wood RJ, Petrucci V, Gunaratnam M, Hughes SM, Buluwela L, Turlais F, Neidle S, Meyer-Almes FJ, White AJ, Fuchter MJ: Defining the mechanism of action and enzymatic selectivity of psammaplin A against its epigenetic targets. J Med Chem. 2012 Feb 23;55(4):1731-50. doi: 10.1021/jm2016182. Epub 2012 Feb 9. [22280363 ]
3. Hobley G, McKelvie JC, Harmer JE, Howe J, Oyston PC, Roach PL: Development of rationally designed DNA N6 adenine methyltransferase inhibitors. Bioorg Med Chem Lett. 2012 May 1;22(9):3079-82. doi: 10.1016/j.bmcl.2012.03.072. Epub 2012 Mar 27. [22483584 ]
4. Saavedra OM, Isakovic L, Llewellyn DB, Zhan L, Bernstein N, Claridge S, Raeppel F, Vaisburg A, Elowe N, Petschner AJ, Rahil J, Beaulieu N, MacLeod AR, Delorme D, Besterman JM, Wahhab A: SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes. Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28. [19362833 ]
5. Kuck D, Singh N, Lyko F, Medina-Franco JL: Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9. doi: 10.1016/j.bmc.2009.11.050. Epub 2009 Nov 27. [20006515 ]
6. Castellano S, Kuck D, Viviano M, Yoo J, Lopez-Vallejo F, Conti P, Tamborini L, Pinto A, Medina-Franco JL, Sbardella G: Synthesis and biochemical evaluation of delta(2)-isoxazoline derivatives as DNA methyltransferase 1 inhibitors. J Med Chem. 2011 Nov 10;54(21):7663-77. doi: 10.1021/jm2010404. Epub 2011 Oct 7. [21958292 ]

General Function:

O-methyltransferase activity

Specific Function:

Putative O-methyltransferase.

Gene Name:

COMTD1

Uniprot ID:

Q86VU5

Molecular Weight:

28808.225 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Unmethylated cpg binding

Specific Function:

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1.

Gene Name:

DNMT3B

Uniprot ID:

Q9UBC3

Molecular Weight:

95750.18 Da

References

1. Isakovic L, Saavedra OM, Llewellyn DB, Claridge S, Zhan L, Bernstein N, Vaisburg A, Elowe N, Petschner AJ, Rahil J, Beaulieu N, Gauthier F, MacLeod AR, Delorme D, Besterman JM, Wahhab A: Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors. Bioorg Med Chem Lett. 2009 May 15;19(10):2742-6. doi: 10.1016/j.bmcl.2009.03.132. Epub 2009 Mar 28. [19364644 ]
2. Kuck D, Singh N, Lyko F, Medina-Franco JL: Novel and selective DNA methyltransferase inhibitors: Docking-based virtual screening and experimental evaluation. Bioorg Med Chem. 2010 Jan 15;18(2):822-9. doi: 10.1016/j.bmc.2009.11.050. Epub 2009 Nov 27. [20006515 ]
3. Saavedra OM, Isakovic L, Llewellyn DB, Zhan L, Bernstein N, Claridge S, Raeppel F, Vaisburg A, Elowe N, Petschner AJ, Rahil J, Beaulieu N, MacLeod AR, Delorme D, Besterman JM, Wahhab A: SAR around (l)-S-adenosyl-l-homocysteine, an inhibitor of human DNA methyltransferase (DNMT) enzymes. Bioorg Med Chem Lett. 2009 May 15;19(10):2747-51. doi: 10.1016/j.bmcl.2009.03.113. Epub 2009 Mar 28. [19362833 ]

General Function:

Methyltransferase activity

Specific Function:

Not Available

Gene Name:

GAMT

Uniprot ID:

Q14353

Molecular Weight:

26317.925 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Protein-l-isoaspartate (d-aspartate) o-methyltransferase activity

Specific Function:

Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein.

Gene Name:

PCMT1

Uniprot ID:

P22061

Molecular Weight:

24636.21 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Transcription factor binding

Specific Function:

Histone methyltransferase. Methylates 'Lys-79' of histone H3. Nucleosomes are preferred as substrate compared to free histones. Binds to DNA.

Gene Name:

DOT1L

Uniprot ID:

Q8TEK3

Molecular Weight:

184851.18 Da

References

1. Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, Cheng G, Chen P, Dong S, Song Y: Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J Med Chem. 2012 Sep 27;55(18):8066-74. Epub 2012 Sep 6. [22924785 ]
2. Yu W, Smil D, Li F, Tempel W, Fedorov O, Nguyen KT, Bolshan Y, Al-Awar R, Knapp S, Arrowsmith CH, Vedadi M, Brown PJ, Schapira M: Bromo-deaza-SAH: a potent and selective DOT1L inhibitor. Bioorg Med Chem. 2013 Apr 1;21(7):1787-94. doi: 10.1016/j.bmc.2013.01.049. Epub 2013 Jan 30. [23433670 ]

General Function:

Phenylethanolamine n-methyltransferase activity

Specific Function:

Converts noradrenaline to adrenaline.

Gene Name:

PNMT

Uniprot ID:

P11086

Molecular Weight:

30854.745 Da

References

1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

Protein-arginine omega-n asymmetric methyltransferase activity

Specific Function:

Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, PIAS1, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15 and EWS. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. Together with dimethylated PIAS1, represses STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity.

Gene Name:

PRMT1

Uniprot ID:

Q99873

Molecular Weight:

41515.2 Da

References

1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
2. Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, Cheng G, Chen P, Dong S, Song Y: Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J Med Chem. 2012 Sep 27;55(18):8066-74. Epub 2012 Sep 6. [22924785 ]

General Function:

Diphthine synthase activity

Specific Function:

S-adenosyl-L-methionine-dependent methyltransferase that catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester. The four successive methylation reactions represent the second step of diphthamide biosynthesis.

Gene Name:

DPH5

Uniprot ID:

Q9H2P9

Molecular Weight:

31651.17 Da

References

1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Glycine n-methyltransferase activity

Specific Function:

Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.

Gene Name:

GNMT

Uniprot ID:

Q14749

Molecular Weight:

32742.0 Da

References

1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Histamine n-methyltransferase activity

Specific Function:

Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.

Gene Name:

HNMT

Uniprot ID:

P50135

Molecular Weight:

33294.765 Da

References

1. Houston DM, Matuszewska B, Borchardt RT: Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 10. Base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine. J Med Chem. 1985 Apr;28(4):478-82. [3981540 ]

General Function:

Transcription regulatory region dna binding

Specific Function:

Methylates (mono- and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in several proteins involved in DNA packaging, transcription regulation, pre-mRNA splicing, and mRNA stability. Recruited to promoters upon gene activation together with histone acetyltransferases from EP300/P300 and p160 families, methylates histone H3 at 'Arg-17' (H3R17me), forming mainly asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling. During nuclear hormone receptor activation and TCF7L2/TCF4 activation, acts synergically with EP300/P300 and either one of the p160 histone acetyltransferases NCOA1/SRC1, NCOA2/GRIP1 and NCOA3/ACTR or CTNNB1/beta-catenin to activate transcription. During myogenic transcriptional activation, acts together with NCOA3/ACTR as a coactivator for MEF2C. During monocyte inflammatory stimulation, acts together with EP300/P300 as a coactivator for NF-kappa-B. Acts as coactivator for PPARG, promotes adipocyte differentiation and the accumulation of brown fat tissue. Plays a role in the regulation of pre-mRNA alternative splicing by methylation of splicing factors. Also seems to be involved in p53/TP53 transcriptional activation. Methylates EP300/P300, both at 'Arg-2142', which may loosen its interaction with NCOA2/GRIP1, and at 'Arg-580' and 'Arg-604' in the KIX domain, which impairs its interaction with CREB and inhibits CREB-dependent transcriptional activation. Also methylates arginine residues in RNA-binding proteins PABPC1, ELAVL1 and ELAV4, which may affect their mRNA-stabilizing properties and the half-life of their target mRNAs.

Gene Name:

CARM1

Uniprot ID:

Q86X55

Molecular Weight:

65853.185 Da

References

1. Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, Cheng G, Chen P, Dong S, Song Y: Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J Med Chem. 2012 Sep 27;55(18):8066-74. Epub 2012 Sep 6. [22924785 ]

General Function:

Zinc ion binding

Specific Function:

Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. Also weakly methylates histone H1 (in vitro). H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes, such as repression of MYOD1-stimulated differentiation, regulation of the control switch for exiting the cell cycle and entering differentiation, repression by the PML-RARA fusion protein, BMP-induced repression, repression of switch recombination to IgA and regulation of telomere length. Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Recruited by the large PER complex to the E-box elements of the circadian target genes such as PER2 itself or PER1, contributes to the conversion of local chromatin to a heterochromatin-like repressive state through H3 'Lys-9' trimethylation.

Gene Name:

SUV39H1

Uniprot ID:

O43463

Molecular Weight:

47907.065 Da

References

1. Anglin JL, Deng L, Yao Y, Cai G, Liu Z, Jiang H, Cheng G, Chen P, Dong S, Song Y: Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L. J Med Chem. 2012 Sep 27;55(18):8066-74. Epub 2012 Sep 6. [22924785 ]

General Function:

Thioether s-methyltransferase activity

Specific Function:

Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds (By similarity). Catalyzes the N-methylation of tryptamine and structurally related compounds.

Gene Name:

INMT

Uniprot ID:

O95050

Molecular Weight:

28890.75 Da

References

1. Benghiat E, Crooks PA: Multisubstrate adducts as potential inhibitors of S-adenosylmethionine dependent methylases: inhibition of indole N-methyltransferase by (5'-deoxyadenosyl)[3-(3-indolyl)prop-1-yl]methylsulfonium and (5'-deoxyadenosyl)[4-(3-indolyl)but-1-yl]methylsulfonium salts. J Med Chem. 1983 Oct;26(10):1470-7. [6620306 ]

General Function:

Protein-arginine omega-n asymmetric methyltransferase activity

Specific Function:

Methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues in some proteins.

Gene Name:

PRMT3

Uniprot ID:

O60678

Molecular Weight:

59875.63 Da

References

1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]

General Function:

Protein-lysine n-methyltransferase activity

Specific Function:

Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.

Gene Name:

SETD7

Uniprot ID:

Q8WTS6

Molecular Weight:

40720.595 Da

General Function:

Trna methyltransferase activity

Specific Function:

Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).

Gene Name:

TRDMT1

Uniprot ID:

O14717

Molecular Weight:

44596.17 Da