9.B.35 The Putative Thyroxine-Transporting Transthyretin (Transthyretin) Family
Transthyretin is a thyroid hormone (thyroxine) binding protein that may function in the transport of thyroxine from the blood stream to the brain across the mammalian blood brain barrier of the choroid plexus. It is most abundant in this tissue but is also found in liver and other tissues. The transthyretin precursor is also known as amyloidosis type I prealbumin. There are amylogenic transthyretin variants that may be important in Alzheimer's disease. These mammalian proteins may also bind vitamin A/retinol binding proteins. Homologues are found in birds, amphibians, worms, yeast and bacteria. An example of a bacterial homologue is the periplasmic YedX protein of E. coli (137aas; spP76341). Based on 3-D structures, two dimer pairs of the mammalian proteins are each believed to form internal channels that are the binding sites for thyroxine. Less than 1% of plasma prealbumin is believed to be involved in thyroxine transport. Numerous references are provided under Swiss Prot acc #P02767. Distant bacterial homologues have been identified (see 9.B.35.2.1). These bacterial homologues may belong to the Peptidase M14NE-CP-C_like superfamily.
The proposed transport reaction catalyzed by the transthyretin channel is:
Thyroxine (blood) (and other compounds) → Thyroxine (brain) (and other compounds)
Hydroxisourate hydrolase of Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)
2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline decarboxylase, Ttl, of 324 aas. Involved in the last two steps of the degradation of uric acid, i.e., the hydrolysis of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) and its stereoselective decarboxylation to (S)-allantoin.
Ttl of Arabidopsis thaliana (Mouse-ear cress)
Transthyritin-like protein, PucM. A probable hydrolase in the uredio pathway; not a transporter (Jung et al. 2006; Doniselli et al. 2015).
PucM of Bacillus subtilis (O32142)
Putative HIUase/transthyretin family protein of126 aas
Transthyretin homologue of Roseobacter litoralis