DEFINITION
Transthyretin - TTR is a serum and cerebrospinal fluid carrier of the thyroid hormone thyroxine (T4) and retinol. This is how transthyretin gained its name, trans ports thy roxine and retin ol. Highly expressed in choroid plexus epithelial cells. Detected in retina pigment epithelium and liver.
Thyroxine-binding globulin - TBG is a globulin that binds thyroid hormones in circulation. Expressed by the liver and secreted in plasma. It is one of three transport proteins (along with transthyretin and serum albumin) responsible for carrying the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream. Of these three proteins, TBG has the highest affinity for T4 and T3 but is present in the lowest concentration. Despite its low concentration, TBG carries the majority of T4 in the blood plasma. Due to the very low concentration of T4 and T3 in the blood, TBG is rarely more than 25% saturated with its ligand. Unlike transthyretin and albumin, TBG has a single binding site for T4/T3. TBG is synthesized primarily in the liver as a 54-kDa protein. In terms of genomics, TBG is a serpin; however, it has no inhibitory function like many other members of this class of proteins.
Serum Albumin
Evolutionary changes to transthyretin: evolution of transthyretin biosynthesis, 2009
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
TTHY_HUMAN : Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Tetramer dissociation and partial unfolding leads to the formation of aggregates and amyloid fibrils. Small molecules that occupy at least one of the thyroid hormone binding sites stabilize the tetramer, and thereby stabilize the native state and protect against misfolding and the formation of amyloid fibrils.
Two binding sites for thyroxine are located in the channel. Less than 1% of plasma prealbumin molecules are normally involved in thyroxine transport. L-thyroxine binds to the transthyretin by an order of magnitude stronger than does the triiodo-L-thyronine. Thyroxine-binding globulin is the major carrier protein for thyroid hormones in man.
About 40% of plasma transthyretin circulates in a tight protein-protein complex with the plasma retinol-binding protein (RBP). The formation of the complex with RBP stabilizes the binding of retinol to RBP and decreases the glomerular filtration and renal catabolism of the relatively small RBP molecule. There is evidence for 2 binding sites for RBP, one possibly being a region that includes Ile-104, located on the outer surface of the transthyretin molecule.
THBG_HUMAN : Major thyroid hormone transport protein in serum. Serpin A7
RET4_HUMAN : Retinol-binding protein that mediates retinol transport in blood plasma (PubMed:5541771). Delivers retinol from the liver stores to the peripheral tissues (Probable). Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane
Each monomer is a 127-residue polypeptide rich in beta sheet structure
TTR is a 55-kDa homotetramer.
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
post-translational modifications
degradation
CELLULAR FUNCTIONS
cellular localization,
biological function
- Enzymes
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
