UniProt functional annotation for P02766



	UniProt functional annotation for P02766

UniProt code: P02766.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. {ECO:0000269|PubMed:3714052}.

Subunit: Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4. {ECO:0000269|PubMed:10052934, ECO:0000269|PubMed:11243784, ECO:0000269|PubMed:11560492, ECO:0000269|PubMed:12820260, ECO:0000269|PubMed:14583036, ECO:0000269|PubMed:14711308, ECO:0000269|PubMed:15735344, ECO:0000269|PubMed:15769474, ECO:0000269|PubMed:15826192, ECO:0000269|PubMed:18095641, ECO:0000269|PubMed:18155178, ECO:0000269|PubMed:18811132, ECO:0000269|PubMed:19021760}.

Subcellular location: Secreted. Cytoplasm.

Tissue specificity: Detected in serum and cerebrospinal fluid (at protein level). Highly expressed in choroid plexus epithelial cells. Detected in retina pigment epithelium and liver. {ECO:0000269|PubMed:10328977, ECO:0000269|PubMed:3714052}.

Domain: Each monomer has two 4-stranded beta sheets and the shape of a prolate ellipsoid. Antiparallel beta-sheet interactions link monomers into dimers. A short loop from each monomer forms the main dimer-dimer interaction. These two pairs of loops separate the opposed, convex beta-sheets of the dimers to form an internal channel.

Ptm: Not glycosylated under normal conditions. Following unfolding, caused for example by variant AMYL-TTR 'Gly-38', the cryptic Asn-118 site is exposed and glycosylated by STT3B-containing OST complex, leading to its degradation by the ER-associated degradation (ERAD) pathway. {ECO:0000269|PubMed:14760718, ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19167329}.

Disease: Amyloidosis, transthyretin-related (AMYL-TTR) [MIM:105210]: A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. {ECO:0000269|PubMed:10036587, ECO:0000269|PubMed:10071047, ECO:0000269|PubMed:10211412, ECO:0000269|PubMed:10436378, ECO:0000269|PubMed:10439117, ECO:0000269|PubMed:10611950, ECO:0000269|PubMed:10627135, ECO:0000269|PubMed:10694917, ECO:0000269|PubMed:10842705, ECO:0000269|PubMed:10842718, ECO:0000269|PubMed:10882995, ECO:0000269|PubMed:11243784, ECO:0000269|PubMed:11445644, ECO:0000269|PubMed:11866053, ECO:0000269|PubMed:12050338, ECO:0000269|PubMed:12403615, ECO:0000269|PubMed:12557757, ECO:0000269|PubMed:12771253, ECO:0000269|PubMed:1301926, ECO:0000269|PubMed:1351039, ECO:0000269|PubMed:1362222, ECO:0000269|PubMed:1436517, ECO:0000269|PubMed:1517749, ECO:0000269|PubMed:1520326, ECO:0000269|PubMed:1520336, ECO:0000269|PubMed:15214015, ECO:0000269|PubMed:15217993, ECO:0000269|PubMed:1544214, ECO:0000269|PubMed:15478468, ECO:0000269|PubMed:1570831, ECO:0000269|PubMed:15735344, ECO:0000269|PubMed:16185074, ECO:0000269|PubMed:1656975, ECO:0000269|PubMed:16627944, ECO:0000269|PubMed:1734866, ECO:0000269|PubMed:17453626, ECO:0000269|PubMed:17503405, ECO:0000269|PubMed:17577687, ECO:0000269|PubMed:17635579, ECO:0000269|PubMed:19167329, ECO:0000269|PubMed:1932142, ECO:0000269|PubMed:2046936, ECO:0000269|PubMed:2161654, ECO:0000269|PubMed:23317988, ECO:0000269|PubMed:2363717, ECO:0000269|PubMed:2891727, ECO:0000269|PubMed:3022108, ECO:0000269|PubMed:3135807, ECO:0000269|PubMed:3722385, ECO:0000269|PubMed:3818577, ECO:0000269|PubMed:6487335, ECO:0000269|PubMed:6583672, ECO:0000269|PubMed:6651852, ECO:0000269|PubMed:7655883, ECO:0000269|PubMed:7850982, ECO:0000269|PubMed:7910950, ECO:0000269|PubMed:7914929, ECO:0000269|PubMed:7923855, ECO:0000269|PubMed:8019560, ECO:0000269|PubMed:8038017, ECO:0000269|PubMed:8081397, ECO:0000269|PubMed:8095302, ECO:0000269|PubMed:8133316, ECO:0000269|PubMed:8257997, ECO:0000269|PubMed:8352764, ECO:0000269|PubMed:8382610, ECO:0000269|PubMed:8428915, ECO:0000269|PubMed:8579098, ECO:0000269|PubMed:8990019, ECO:0000269|PubMed:9066351, ECO:0000269|PubMed:9605286, ECO:0000269|PubMed:9733771, ECO:0000269|Ref.90}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Hyperthyroxinemia, dystransthyretinemic (DTTRH) [MIM:145680]: A condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. {ECO:0000269|PubMed:1979335}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Carpal tunnel syndrome 1 (CTS1) [MIM:115430]: A condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis. {ECO:0000269|PubMed:8309582}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: 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.

Miscellaneous: 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.

Miscellaneous: 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.

Similarity: Belongs to the transthyretin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain. {ECO:0000269\|PubMed:3714052}.


Subunit:		Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4. {ECO:0000269\|PubMed:10052934, ECO:0000269\|PubMed:11243784, ECO:0000269\|PubMed:11560492, ECO:0000269\|PubMed:12820260, ECO:0000269\|PubMed:14583036, ECO:0000269\|PubMed:14711308, ECO:0000269\|PubMed:15735344, ECO:0000269\|PubMed:15769474, ECO:0000269\|PubMed:15826192, ECO:0000269\|PubMed:18095641, ECO:0000269\|PubMed:18155178, ECO:0000269\|PubMed:18811132, ECO:0000269\|PubMed:19021760}.
Subcellular location:		Secreted. Cytoplasm.
Tissue specificity:		Detected in serum and cerebrospinal fluid (at protein level). Highly expressed in choroid plexus epithelial cells. Detected in retina pigment epithelium and liver. {ECO:0000269\|PubMed:10328977, ECO:0000269\|PubMed:3714052}.
Domain:		Each monomer has two 4-stranded beta sheets and the shape of a prolate ellipsoid. Antiparallel beta-sheet interactions link monomers into dimers. A short loop from each monomer forms the main dimer-dimer interaction. These two pairs of loops separate the opposed, convex beta-sheets of the dimers to form an internal channel.
Ptm:		Not glycosylated under normal conditions. Following unfolding, caused for example by variant AMYL-TTR 'Gly-38', the cryptic Asn-118 site is exposed and glycosylated by STT3B-containing OST complex, leading to its degradation by the ER-associated degradation (ERAD) pathway. {ECO:0000269\|PubMed:14760718, ECO:0000269\|PubMed:16335952, ECO:0000269\|PubMed:19167329}.
Disease:		Amyloidosis, transthyretin-related (AMYL-TTR) [MIM:105210]: A hereditary generalized amyloidosis due to transthyretin amyloid deposition. Protein fibrils can form in different tissues leading to amyloid polyneuropathies, amyloidotic cardiomyopathy, carpal tunnel syndrome, systemic senile amyloidosis. The disease includes leptomeningeal amyloidosis that is characterized by primary involvement of the central nervous system. Neuropathologic examination shows amyloid in the walls of leptomeningeal vessels, in pia arachnoid, and subpial deposits. Some patients also develop vitreous amyloid deposition that leads to visual impairment (oculoleptomeningeal amyloidosis). Clinical features include seizures, stroke-like episodes, dementia, psychomotor deterioration, variable amyloid deposition in the vitreous humor. {ECO:0000269\|PubMed:10036587, ECO:0000269\|PubMed:10071047, ECO:0000269\|PubMed:10211412, ECO:0000269\|PubMed:10436378, ECO:0000269\|PubMed:10439117, ECO:0000269\|PubMed:10611950, ECO:0000269\|PubMed:10627135, ECO:0000269\|PubMed:10694917, ECO:0000269\|PubMed:10842705, ECO:0000269\|PubMed:10842718, ECO:0000269\|PubMed:10882995, ECO:0000269\|PubMed:11243784, ECO:0000269\|PubMed:11445644, ECO:0000269\|PubMed:11866053, ECO:0000269\|PubMed:12050338, ECO:0000269\|PubMed:12403615, ECO:0000269\|PubMed:12557757, ECO:0000269\|PubMed:12771253, ECO:0000269\|PubMed:1301926, ECO:0000269\|PubMed:1351039, ECO:0000269\|PubMed:1362222, ECO:0000269\|PubMed:1436517, ECO:0000269\|PubMed:1517749, ECO:0000269\|PubMed:1520326, ECO:0000269\|PubMed:1520336, ECO:0000269\|PubMed:15214015, ECO:0000269\|PubMed:15217993, ECO:0000269\|PubMed:1544214, ECO:0000269\|PubMed:15478468, ECO:0000269\|PubMed:1570831, ECO:0000269\|PubMed:15735344, ECO:0000269\|PubMed:16185074, ECO:0000269\|PubMed:1656975, ECO:0000269\|PubMed:16627944, ECO:0000269\|PubMed:1734866, ECO:0000269\|PubMed:17453626, ECO:0000269\|PubMed:17503405, ECO:0000269\|PubMed:17577687, ECO:0000269\|PubMed:17635579, ECO:0000269\|PubMed:19167329, ECO:0000269\|PubMed:1932142, ECO:0000269\|PubMed:2046936, ECO:0000269\|PubMed:2161654, ECO:0000269\|PubMed:23317988, ECO:0000269\|PubMed:2363717, ECO:0000269\|PubMed:2891727, ECO:0000269\|PubMed:3022108, ECO:0000269\|PubMed:3135807, ECO:0000269\|PubMed:3722385, ECO:0000269\|PubMed:3818577, ECO:0000269\|PubMed:6487335, ECO:0000269\|PubMed:6583672, ECO:0000269\|PubMed:6651852, ECO:0000269\|PubMed:7655883, ECO:0000269\|PubMed:7850982, ECO:0000269\|PubMed:7910950, ECO:0000269\|PubMed:7914929, ECO:0000269\|PubMed:7923855, ECO:0000269\|PubMed:8019560, ECO:0000269\|PubMed:8038017, ECO:0000269\|PubMed:8081397, ECO:0000269\|PubMed:8095302, ECO:0000269\|PubMed:8133316, ECO:0000269\|PubMed:8257997, ECO:0000269\|PubMed:8352764, ECO:0000269\|PubMed:8382610, ECO:0000269\|PubMed:8428915, ECO:0000269\|PubMed:8579098, ECO:0000269\|PubMed:8990019, ECO:0000269\|PubMed:9066351, ECO:0000269\|PubMed:9605286, ECO:0000269\|PubMed:9733771, ECO:0000269\|Ref.90}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Hyperthyroxinemia, dystransthyretinemic (DTTRH) [MIM:145680]: A condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities. {ECO:0000269\|PubMed:1979335}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Carpal tunnel syndrome 1 (CTS1) [MIM:115430]: A condition characterized by entrapment of the median nerve within the carpal tunnel. Symptoms include burning pain and paresthesias involving the ventral surface of the hand and fingers which may radiate proximally. Impairment of sensation in the distribution of the median nerve and thenar muscle atrophy may occur. This condition may be associated with repetitive occupational trauma, wrist injuries, amyloid neuropathies, rheumatoid arthritis. {ECO:0000269\|PubMed:8309582}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		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.
Miscellaneous:		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.
Miscellaneous:		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.
Similarity:		Belongs to the transthyretin family. {ECO:0000305}.