Protein Family Models

This family includes transthyretin that is a thyroid hormone-binding protein that transports thyroxine from the bloodstream to the brain. However, most of the sequences listed in this family do not bind thyroid hormones. They are actually enzymes of the purine catabolism that catalyse the conversion of 5-hydroxyisourate (HIU) to OHCU [2,3]. HIU hydrolysis is the original function of the family and is conserved from bacteria to mammals; transthyretins arose by gene duplications in the vertebrate lineage [4]. HIUases are distinguished in the alignment from the conserved C-terminal YRGS sequence. [1]. 8428915. The x-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution. Hamilton JA, Steinrauf LK, Braden BC, Liepnieks J, Benson MD, Holmgren G, Sandgren O, Steen L;. J Biol Chem 1993;268:2416-2424. [2]. 16462750. Completing the uric acid degradation pathway through phylogenetic comparison of whole genomes. Ramazzina I, Folli C, Secchi A, Berni R, Percudani R;. Nat Chem Biol. 2006;2:144-148. [3]. 16098976. Transthyretin-related proteins function to facilitate the hydrolysis of 5-hydroxyisourate, the end product of the uricase reaction. Lee Y, Lee DH, Kho CW, Lee AY, Jang M, Cho S, Lee CH, Lee JS, Myung PK, Park BC, Park SG;. FEBS Lett. 2005;579:4769-4774. [4]. 16952372. Structure of zebra fish HIUase: insights into evolution of an enzyme to a hormone transporter. Zanotti G, Cendron L, Ramazzina I, Folli C, Percudani R, Berni R;. J Mol Biol. 2006;363:1-9. (from Pfam)

Date:

2024-10-16

hydroxyisourate hydrolase catalyzes the hydrolysis of 5-hydroxyisourate (HIU) to 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) in the second step of a three-step ureide pathway

Date:

2017-03-21

Members of this family, hydroxyisourate hydrolase, represent a distinct clade of transthyretin-related proteins. Bacterial members typically are encoded next to ureidoglycolate hydrolase and often near either xanthine dehydrogenase or xanthine/uracil permease genes and have been demonstrated to have hydroxyisourate hydrolase activity [1]. In eukaryotes, a clade separate from the transthyretins (a family of thyroid-hormone binding proteins) has also been shown to have HIU hydrolase activity in urate catabolizing organisms [2]. Transthyretin, then, would appear to be the recently diverged paralog of the more ancient HIUH family.

Gene:

uraH

Date:

2024-05-29