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Human MATE1 (denoted as hMATE1) is enriched in the kidneys, liver, adrenal glands, choroid plexus, and skeletal muscle [5–7]. Similarly, hMATE1 has been detected in salivary glands [8], adipocytes [9], retinal pigment epithelial cells [10], lung bronchial and bronchiolar epithelial cells [11], and dermal fibroblasts [12]. Within the brain, hMATE1 mRNA localizes to capillary endothelial cells [13]. Initial studies of the tissue distribution of mouse Mate1 (denoted as mMate1) revealed predominant expression in kidneys and liver [5, 14]. Additional profiling across mouse tissues extended the distribution of mMate1 protein to include heart, stomach, small intestine, bladder, thyroid, gland, testes, and adrenal gland [15]. Rat Mate1 (denoted as rMate1) was cloned in 2006 and shown to be highly expressed in kidneys, as well as liver, placenta, pancreas, and spleen [16–19].

In contrast, hMATE2 is largely restricted to the kidneys [5]. An alternative kidney splice variant (denoted as hMATE2‐K) was cloned and shown to lack 108 bp [6]. This region codes for an additional 36 amino acids within a predicted intracellular loop—a region that is not observed in mMate2 or rabbit Mate2‐K [20]. Overall, there is 94% identity between hMATE2 and hMATE2‐K and ~50% amino acid identity with hMATE1. Both hMATE2 and hMATE2‐K are expressed within human kidneys [21]. When purified and reconstituted in proteoliposomes, hMATE2 and hMATE2‐K exhibit similar kinetic properties [21]. In addition, a lesser described hMATE2‐B variant has been found in the brain, but this isoform appears to lack transport activity [6].

While there is moderate‐to‐high sequence identity among MATE1/Mate1 orthologs, there appears to be greater divergence for MATE2 with low sequence identity between hMATE2 and mMate2 (38%) [22]. This becomes more evident when viewing the phylogenetic tree for mammalian MATE‐type transporters [22](Fig. 3.1). MATE1 isoforms are found in Class I, whereas primate MATE2 and dog Mate2 are considered members of Class II. Mouse and rat Mate2 are found in Class III [22].