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Table 2 Classification of D. melanogaster Su(var)3-9 mutants, based on structure modelling and comparison with orthologous proteins.

From: The evolution of the histone methyltransferase gene Su(var)3-9 in metazoans includes a fusion with and a re-fission from a functionally unrelated gene

Allele Amino acid sub-stitution Phenotype [6] Conserved in Occurrence of the substitution and compensation [50]; Function of residue
   in vivo (PEV) in vitro (HMTase)   
Class I – absolute conserved residues
2,7 C427Y null null all HMTases zinc coordination [37]
21 E455V Hypo-morph null all HMTases -
31 E455K    all HMTases intramolecular charge interaction [33]
3 R469C   null all HMTases intramolecular charge interaction [33]
27 G491R   null all HMTases Adomet (substrate) binding [32]
12,23 V492E    all HMTases intramolecular hydrophobic interaction [33]
4,5 G509E null null all HMTases structural residue glycine [33]
Class II – compensable deviated residues (CPDs)
30 A437T   null Su(var)3-9, dim5 T in all beetles, compensated by L435G/S
9 C505Y   null Su(var)3-9, G9a, SUVH, SETDB L in Araneus diadematus, compensated by V585A
34 E506K    Su(var)3-9, G9a, SUVH K in Acyrthosiphon pisum, compensation unknown (many substitutions in contact area of the residue)
320 D536N    Su(var)3-9, dim5, G9a N in Dictyostelium discoideum, compensated by Y537G and N538D
32 S562F null null all HMTases L in some G9a proteins, compensated by S599G
13 P571S Hypo-morph Hypo-morph Su(var)3-9 (Drosophila), SUVH, dim5 S in Mus musculus Suv39h2 and in mosquitos, compensated by C572V and H583R; A ribose hydroxyl of the methyltransferase reaction end product AdoHcy interact with the side chain carboxyl of the homologous D202 in Neurospora dim-5 [32]
10 D601N null Hypo-morph most of all HMTases N in mosquitos, Acyrthosiphon pisum and in some other HMTases, compensation ambiguous; involved in formation of lysine (substrate) binding channel [32]
8 N607Y null Hypo-morph Su(var)3-9 (Drosophila) no substitution or residue not conserved
25 P611L Hypo-morph Hypo-morph Su(var)3-9 (Drosophila) no substitution or residue not conserved
319 S616L    Su(var)3-9 (Drosophila) no substitution or residue not conserved
22 L634F Hypo-morph Hypo-morph Su(var)3-9, dim5, SETDB F in Enallagma cyathigerum, compensated by F635M
Class III – Uncompensated gain of function alleles
ptn R529S Hyper-morph Hyper-morph Su(var)3-9 S in three fishes and in Acyrthosiphon pisum, local compensation is excluded; the side chain of the homologous L317 in Neurospora dim-5 is involved in HMTase activity [32]