Over the 31 first positions of the cytoplasmic domain, 20 are completely conserved and 5 contain conservative substitutions (Fig. 1A).
Of the five MST3 residues on β4 and β5, four are completely conserved (Tyr85, Ser88, Leu95) while Leu90 is conservatively substituted by Val in OSR1 and SPAK.
Of the six MST3 residues on β3 and αC that interact with MO25β, three are completely conserved (Leu57, Glu58 and Ile71) and two are conservatively substituted in OSR1 and SPAK (Asp62 (as Thr) and Ile64 (as Met)).
Particularly G and K are completely conserved at position 6 and 7 respectively, along with higher conservation for G at the first position as depicted by the sequence logo (see Figure 2G).
The amino acids lining the co-substrate binding pocket are completely conserved in MDHs from different species of human, primate and rodent malaria parasites.
Structural comparison shows that two glycines are completely conserved in the family, in addition to the two catalytic glutamates and six other conserved residues previously identified.
The seed regions of miR-495 and the seed-recognizing sites in the JAM-A 3′-UTR are indicated in red, and all nucleotides in seed-recognizing sites are completely conserved across several species.
In the other Eurotiales (Pmarn, Tstip and Pchry), five of these cysteines are completely conserved.
As these sequences are completely conserved, all of these epitopes are found in all reported WNV strains.
Furthermore, this motif and the adjacent residues are completely conserved in all VHL proteins from different species, including humans, monkey, dog, rat and mice (supplementary information, Figure S1).
It encodes a protein of 349 amino acids with 43% sequence identity to Cyr61, and all 38 cysteines in CTGF and Cyr61 are completely conserved.
