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In an effort to shed more light on the early evolutionary history of the heavy-chain subunits of heteromeric amino acid transporters (hcHATs) rBAT and 4F2hc within the α-amylase family GH13, a bioinformatics study was undertaken. The focus of the study was on a detailed sequence comparison of rBAT and 4F2hc proteins from as wide as possible taxonomic spectrum and enzyme specificities from the α-amylase family. The GH13 enzymes were selected from the so-called GH13 oligo-1,6-glucosidase and neopullulanase subfamilies that represent the α-amylase family enzyme groups most closely related to hcHATs. Within this study, more than 30 hcHAT-like proteins, designated here as hcHAT1 and hcHAT2 groups, were identified in basal Metazoa. Of the GH13 catalytic triad, only the catalytic nucleophile (aspartic acid 199 of the oligo-1,6-glucosidase) could have its counterpart in some 4F2hc proteins, whereas most rBATs contain the correspondences for the entire GH13 catalytic triad. Moreover, the 4F2hc proteins lack not only domain B typical for GH13 enzymes, but also a stretch of ∼ 40 amino acid residues succeeding the β4-strand of the catalytic TIM barrel. rBATs have the entire domain B as well as longer loop 4. The higher sequence–structural similarity between rBATs and GH13 enzymes was reflected in the evolutionary tree. At present it is necessary to consider two different scenarios on how the chordate rBAT and 4F2hc proteins might have evolved. The GH13-like protein from the cnidarian Nematostella vectensis might nowadays represent a protein close to the eventual ancestor of the hcHAT proteins within the GH13 family.