P02766 · TTHY_HUMAN
- ProteinTransthyretin
- GeneTTR
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids147 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
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.
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.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | azurophil granule lumen | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Molecular Function | hormone activity | |
Molecular Function | identical protein binding | |
Molecular Function | thyroid hormone binding | |
Biological Process | purine nucleobase metabolic process |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTransthyretin
- Alternative names
Gene names
- Community suggested namesTTR
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP02766
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Amyloidosis, hereditary systemic 1 (AMYLD1)
- Note
- DescriptionA form of hereditary systemic amyloidosis, a disorder characterized by amyloid deposition in multiple tissues resulting in a wide clinical spectrum. AMYLD1 is an autosomal dominant form 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.
- See alsoMIM:105210
Natural variants in AMYLD1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_007547 | 30 | C>R | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918083 | |
VAR_038959 | 32 | L>P | in AMYLD1; dbSNP:rs121918094 | |
VAR_007548 | 38 | D>E | in AMYLD1; amyloid polyneuropathy | |
VAR_007549 | 38 | D>G | in AMYLD1; leptomeningeal amyloidosis; leads to unfolding and exposure of N-118 to glycosylation by STT3B and subsequent degradation by the ERAD pathway; dbSNP:rs121918098 | |
VAR_007550 | 40 | V>I | in AMYLD1; late-onset amyloid polyneuropathy with carpal tunnel syndrome; dbSNP:rs121918093 | |
VAR_038961 | 43 | S>N | in AMYLD1 | |
VAR_007551 | 44 | P>S | in AMYLD1; amyloid polyneuropathy; dbSNP:rs11541790 | |
VAR_010658 | 48 | V>M | in AMYLD1; amyloid polyneuropathy | |
VAR_007552 | 50 | V>A | in AMYLD1; amyloid polyneuropathy; dbSNP:rs79977247 | |
VAR_038962 | 50 | V>G | in AMYLD1; dbSNP:rs79977247 | |
VAR_007553 | 50 | V>L | in AMYLD1; amyloid polyneuropathy; dbSNP:rs28933979 | |
VAR_007554 | 50 | V>M | in AMYLD1; amyloid polyneuropathy; by far the most frequent mutation; dbSNP:rs28933979 | |
VAR_007555 | 53 | F>I | in AMYLD1; Jewish 'SKO' amyloid polyneuropathy; dbSNP:rs121918068 | |
VAR_007556 | 53 | F>L | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918068 | |
VAR_038964 | 53 | F>V | in AMYLD1; amyloid polyneuropathy | |
VAR_038965 | 54 | R>T | in AMYLD1 | |
VAR_038966 | 55 | K>N | in AMYLD1; amyloid polyneuropathy | |
VAR_007557 | 56 | A>P | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918077 | |
VAR_038967 | 58 | D>A | in AMYLD1 | |
VAR_038968 | 58 | D>V | in AMYLD1 | |
VAR_038969 | 61 | W>L | in AMYLD1 | |
VAR_038970 | 62 | E>D | in AMYLD1; dbSNP:rs11541796 | |
VAR_007558 | 62 | E>G | in AMYLD1; amyloid polyneuropathy; dbSNP:rs11541796 | |
VAR_038971 | 64 | F>S | in AMYLD1; dbSNP:rs104894665 | |
VAR_007559 | 65 | A>D | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs730881169 | |
VAR_038972 | 65 | A>S | in AMYLD1 | |
VAR_007560 | 65 | A>T | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918078 | |
VAR_007561 | 67 | G>A | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918090 | |
VAR_038973 | 67 | G>E | in AMYLD1 | |
VAR_007562 | 67 | G>R | in AMYLD1; amyloid polyneuropathy; dbSNP:rs387906523 | |
VAR_007563 | 67 | G>V | in AMYLD1; amyloid polyneuropathy with carpal tunnel syndrome | |
VAR_007564 | 69 | T>A | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918081 | |
VAR_038974 | 69 | T>I | in AMYLD1 | |
VAR_007565 | 70 | S>I | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918080 | |
VAR_007566 | 70 | S>R | in AMYLD1; amyloid polyneuropathy; dbSNP:rs386134269 | |
VAR_007567 | 72 | S>P | in AMYLD1; amyloid polyneuropathy | |
VAR_038975 | 73 | G>E | in AMYLD1; dbSNP:rs121918097 | |
VAR_007568 | 74 | E>G | in AMYLD1; amyloid polyneuropathy | |
VAR_038976 | 74 | E>K | in AMYLD1; early-onset amyloid polyneuropathy | |
VAR_007569 | 75 | L>P | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918079 | |
VAR_038977 | 75 | L>Q | in AMYLD1 | |
VAR_007570 | 78 | L>H | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918069 | |
VAR_007571 | 78 | L>R | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918069 | |
VAR_007572 | 79 | T>K | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs730881163 | |
VAR_007573 | 80 | T>A | in AMYLD1; amyloid polyneuropathy and cardiomyopathy; dbSNP:rs121918070 | |
VAR_038978 | 81 | E>G | in AMYLD1 | |
VAR_007574 | 81 | E>K | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918086 | |
VAR_007575 | 84 | F>L | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918091 | |
VAR_007576 | 88 | I>L | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918085 | |
VAR_007577 | 89 | Y>H | in AMYLD1; leptomeningeal amyloidosis; vitreous amyloid in some patients; dbSNP:rs121918100 | |
VAR_007578 | 90 | K>N | in AMYLD1; amyloid polyneuropathy; dbSNP:rs267607160 | |
VAR_007579 | 91 | V>A | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918084 | |
VAR_007580 | 93 | I>V | in AMYLD1; amyloid polyneuropathy | |
VAR_007582 | 97 | S>Y | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918071 | |
VAR_038979 | 98 | Y>F | in AMYLD1; dbSNP:rs958191819 | |
VAR_007583 | 104 | I>N | in AMYLD1; vitrous amyloid | |
VAR_007584 | 104 | I>S | in AMYLD1; amyloid polyneuropathy; almost no RBP binding; dbSNP:rs121918072 | |
VAR_038980 | 104 | I>T | in AMYLD1 | |
VAR_010659 | 109 | E>K | in AMYLD1; amyloid polyneuropathy | |
VAR_007585 | 109 | E>Q | in AMYLD1; amyloid polyneuropathy and cardiomyopathy; dbSNP:rs121918082 | |
VAR_007587 | 111 | A>S | in AMYLD1; amyloid polyneuropathy | |
VAR_007588 | 117 | A>G | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918087 | |
VAR_038982 | 117 | A>S | in AMYLD1; dbSNP:rs267607161 | |
VAR_038984 | 126 | T>N | in AMYLD1; dbSNP:rs1456101911 | |
VAR_038985 | 127 | I>M | in AMYLD1 | |
VAR_007592 | 127 | I>V | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918089 | |
VAR_007594 | 131 | L>M | in AMYLD1; dbSNP:rs121918073 | |
VAR_007595 | 134 | Y>C | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918075 | |
VAR_007596 | 136 | Y>S | in AMYLD1; amyloid polyneuropathy; dbSNP:rs730881167 | |
VAR_038986 | 140 | A>S | in AMYLD1; dbSNP:rs876658108 | |
VAR_038987 | 142 | V>A | in AMYLD1 | |
VAR_007600 | 142 | V>I | in AMYLD1; dbSNP:rs76992529 | |
VAR_038988 | 144 | N>S | in AMYLD1; uncertain significance; dbSNP:rs144965179 |
Hyperthyroxinemia, dystransthyretinemic (DTTRH)
- Note
- DescriptionA condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.
- See alsoMIM:145680
Natural variants in DTTRH
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_007593 | 129 | A>T | in DTTRH; increased affinity for thyroxine; dbSNP:rs267607159 |
Carpal tunnel syndrome 1 (CTS1)
- Note
- DescriptionA 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.
- See alsoMIM:115430
Natural variants in CTS1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_007598 | 134 | Y>H | in CTS1; amyloid deposit on carpal tunnel; patients show no other abnormalities; dbSNP:rs121918088 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_007546 | 26 | in dbSNP:rs1800458 | |||
Sequence: G → S | ||||||
Natural variant | VAR_007547 | 30 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918083 | |||
Sequence: C → R | ||||||
Natural variant | VAR_038959 | 32 | in AMYLD1; dbSNP:rs121918094 | |||
Sequence: L → P | ||||||
Natural variant | VAR_038960 | 33 | ||||
Sequence: M → I | ||||||
Natural variant | VAR_007548 | 38 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: D → E | ||||||
Natural variant | VAR_007549 | 38 | in AMYLD1; leptomeningeal amyloidosis; leads to unfolding and exposure of N-118 to glycosylation by STT3B and subsequent degradation by the ERAD pathway; dbSNP:rs121918098 | |||
Sequence: D → G | ||||||
Natural variant | VAR_007550 | 40 | in AMYLD1; late-onset amyloid polyneuropathy with carpal tunnel syndrome; dbSNP:rs121918093 | |||
Sequence: V → I | ||||||
Natural variant | VAR_038961 | 43 | in AMYLD1 | |||
Sequence: S → N | ||||||
Natural variant | VAR_007551 | 44 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs11541790 | |||
Sequence: P → S | ||||||
Natural variant | VAR_010658 | 48 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: V → M | ||||||
Natural variant | VAR_007552 | 50 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs79977247 | |||
Sequence: V → A | ||||||
Natural variant | VAR_038962 | 50 | in AMYLD1; dbSNP:rs79977247 | |||
Sequence: V → G | ||||||
Natural variant | VAR_007553 | 50 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs28933979 | |||
Sequence: V → L | ||||||
Natural variant | VAR_007554 | 50 | in AMYLD1; amyloid polyneuropathy; by far the most frequent mutation; dbSNP:rs28933979 | |||
Sequence: V → M | ||||||
Natural variant | VAR_038963 | 53 | in a patient with amyloidosis | |||
Sequence: F → C | ||||||
Natural variant | VAR_007555 | 53 | in AMYLD1; Jewish 'SKO' amyloid polyneuropathy; dbSNP:rs121918068 | |||
Sequence: F → I | ||||||
Natural variant | VAR_007556 | 53 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918068 | |||
Sequence: F → L | ||||||
Natural variant | VAR_038964 | 53 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: F → V | ||||||
Natural variant | VAR_038965 | 54 | in AMYLD1 | |||
Sequence: R → T | ||||||
Natural variant | VAR_038966 | 55 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: K → N | ||||||
Natural variant | VAR_007557 | 56 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918077 | |||
Sequence: A → P | ||||||
Natural variant | VAR_038967 | 58 | in AMYLD1 | |||
Sequence: D → A | ||||||
Natural variant | VAR_038968 | 58 | in AMYLD1 | |||
Sequence: D → V | ||||||
Natural variant | VAR_038969 | 61 | in AMYLD1 | |||
Sequence: W → L | ||||||
Natural variant | VAR_038970 | 62 | in AMYLD1; dbSNP:rs11541796 | |||
Sequence: E → D | ||||||
Natural variant | VAR_007558 | 62 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs11541796 | |||
Sequence: E → G | ||||||
Natural variant | VAR_038971 | 64 | in AMYLD1; dbSNP:rs104894665 | |||
Sequence: F → S | ||||||
Natural variant | VAR_007559 | 65 | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs730881169 | |||
Sequence: A → D | ||||||
Natural variant | VAR_038972 | 65 | in AMYLD1 | |||
Sequence: A → S | ||||||
Natural variant | VAR_007560 | 65 | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918078 | |||
Sequence: A → T | ||||||
Natural variant | VAR_007561 | 67 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918090 | |||
Sequence: G → A | ||||||
Natural variant | VAR_038973 | 67 | in AMYLD1 | |||
Sequence: G → E | ||||||
Natural variant | VAR_007562 | 67 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs387906523 | |||
Sequence: G → R | ||||||
Natural variant | VAR_007563 | 67 | in AMYLD1; amyloid polyneuropathy with carpal tunnel syndrome | |||
Sequence: G → V | ||||||
Natural variant | VAR_007564 | 69 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918081 | |||
Sequence: T → A | ||||||
Natural variant | VAR_038974 | 69 | in AMYLD1 | |||
Sequence: T → I | ||||||
Natural variant | VAR_007565 | 70 | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918080 | |||
Sequence: S → I | ||||||
Natural variant | VAR_007566 | 70 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs386134269 | |||
Sequence: S → R | ||||||
Natural variant | VAR_007567 | 72 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: S → P | ||||||
Natural variant | VAR_038975 | 73 | in AMYLD1; dbSNP:rs121918097 | |||
Sequence: G → E | ||||||
Natural variant | VAR_007568 | 74 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: E → G | ||||||
Natural variant | VAR_038976 | 74 | in AMYLD1; early-onset amyloid polyneuropathy | |||
Sequence: E → K | ||||||
Natural variant | VAR_007569 | 75 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918079 | |||
Sequence: L → P | ||||||
Natural variant | VAR_038977 | 75 | in AMYLD1 | |||
Sequence: L → Q | ||||||
Natural variant | VAR_007570 | 78 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918069 | |||
Sequence: L → H | ||||||
Natural variant | VAR_007571 | 78 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918069 | |||
Sequence: L → R | ||||||
Natural variant | VAR_007572 | 79 | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs730881163 | |||
Sequence: T → K | ||||||
Natural variant | VAR_007573 | 80 | in AMYLD1; amyloid polyneuropathy and cardiomyopathy; dbSNP:rs121918070 | |||
Sequence: T → A | ||||||
Natural variant | VAR_038978 | 81 | in AMYLD1 | |||
Sequence: E → G | ||||||
Natural variant | VAR_007574 | 81 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918086 | |||
Sequence: E → K | ||||||
Natural variant | VAR_007575 | 84 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918091 | |||
Sequence: F → L | ||||||
Natural variant | VAR_007576 | 88 | in AMYLD1; amyloid cardiomyopathy; dbSNP:rs121918085 | |||
Sequence: I → L | ||||||
Natural variant | VAR_007577 | 89 | in AMYLD1; leptomeningeal amyloidosis; vitreous amyloid in some patients; dbSNP:rs121918100 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_007578 | 90 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs267607160 | |||
Sequence: K → N | ||||||
Natural variant | VAR_007579 | 91 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918084 | |||
Sequence: V → A | ||||||
Natural variant | VAR_007580 | 93 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: I → V | ||||||
Natural variant | VAR_007581 | 94 | in dbSNP:rs730881164 | |||
Sequence: D → H | ||||||
Natural variant | VAR_007582 | 97 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918071 | |||
Sequence: S → Y | ||||||
Natural variant | VAR_038979 | 98 | in AMYLD1; dbSNP:rs958191819 | |||
Sequence: Y → F | ||||||
Natural variant | VAR_007583 | 104 | in AMYLD1; vitrous amyloid | |||
Sequence: I → N | ||||||
Natural variant | VAR_007584 | 104 | in AMYLD1; amyloid polyneuropathy; almost no RBP binding; dbSNP:rs121918072 | |||
Sequence: I → S | ||||||
Natural variant | VAR_038980 | 104 | in AMYLD1 | |||
Sequence: I → T | ||||||
Mutagenesis | 107 | Loss of tetramerization; when associated with M-130. | ||||
Sequence: F → M | ||||||
Natural variant | VAR_010659 | 109 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: E → K | ||||||
Natural variant | VAR_007585 | 109 | in AMYLD1; amyloid polyneuropathy and cardiomyopathy; dbSNP:rs121918082 | |||
Sequence: E → Q | ||||||
Natural variant | VAR_007586 | 110 | in dbSNP:rs121918074 | |||
Sequence: H → N | ||||||
Natural variant | VAR_007587 | 111 | in AMYLD1; amyloid polyneuropathy | |||
Sequence: A → S | ||||||
Natural variant | VAR_038981 | 114 | in a patient with amyloidosis | |||
Sequence: V → A | ||||||
Natural variant | VAR_007588 | 117 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918087 | |||
Sequence: A → G | ||||||
Natural variant | VAR_038982 | 117 | in AMYLD1; dbSNP:rs267607161 | |||
Sequence: A → S | ||||||
Natural variant | VAR_007589 | 121 | in dbSNP:rs755337715 | |||
Sequence: G → S | ||||||
Natural variant | VAR_007590 | 122 | ||||
Sequence: P → R | ||||||
Natural variant | VAR_007591 | 124 | in dbSNP:rs745834030 | |||
Sequence: R → C | ||||||
Natural variant | VAR_038983 | 124 | in dbSNP:rs121918095 | |||
Sequence: R → H | ||||||
Natural variant | VAR_038984 | 126 | in AMYLD1; dbSNP:rs1456101911 | |||
Sequence: T → N | ||||||
Natural variant | VAR_038985 | 127 | in AMYLD1 | |||
Sequence: I → M | ||||||
Natural variant | VAR_007592 | 127 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918089 | |||
Sequence: I → V | ||||||
Natural variant | VAR_007593 | 129 | in DTTRH; increased affinity for thyroxine; dbSNP:rs267607159 | |||
Sequence: A → T | ||||||
Mutagenesis | 130 | Loss of tetramerization; when associated with M-107. | ||||
Sequence: L → M | ||||||
Natural variant | VAR_007594 | 131 | in AMYLD1; dbSNP:rs121918073 | |||
Sequence: L → M | ||||||
Natural variant | VAR_007595 | 134 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs121918075 | |||
Sequence: Y → C | ||||||
Natural variant | VAR_007598 | 134 | in CTS1; amyloid deposit on carpal tunnel; patients show no other abnormalities; dbSNP:rs121918088 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_007596 | 136 | in AMYLD1; amyloid polyneuropathy; dbSNP:rs730881167 | |||
Sequence: Y → S | ||||||
Natural variant | VAR_007597 | 136 | requires 2 nucleotide substitutions | |||
Sequence: Y → V | ||||||
Natural variant | VAR_007599 | 139 | in Chicago variant; dbSNP:rs28933981 | |||
Sequence: T → M | ||||||
Natural variant | VAR_038986 | 140 | in AMYLD1; dbSNP:rs876658108 | |||
Sequence: A → S | ||||||
Natural variant | VAR_038987 | 142 | in AMYLD1 | |||
Sequence: V → A | ||||||
Natural variant | VAR_007600 | 142 | in AMYLD1; dbSNP:rs76992529 | |||
Sequence: V → I | ||||||
Natural variant | VAR_038988 | 144 | in AMYLD1; uncertain significance; dbSNP:rs144965179 | |||
Sequence: N → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 278 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, modified residue, modified residue (large scale data), glycosylation.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Signal | 1-20 | UniProt | |||||
Sequence: MASHRLLLLCLAGLVFVSEA | |||||||
Chain | PRO_0000035755 | 21-147 | UniProt | Transthyretin | |||
Sequence: GPTGTGESKCPLMVKVLDAVRGSPAINVAVHVFRKAADDTWEPFASGKTSESGELHGLTTEEEFVEGIYKVEIDTKSYWKALGISPFHEHAEVVFTANDSGPRRYTIAALLSPYSYSTTAVVTNPKE | |||||||
Modified residue | 30 | UniProt | Sulfocysteine | ||||
Sequence: C | |||||||
Modified residue | 62 | UniProt | 4-carboxyglutamate; in a patient with Moyamoya disease | ||||
Sequence: E | |||||||
Modified residue | 72 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 72 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Glycosylation | 118 | UniProt | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
Not glycosylated under normal conditions. Following unfolding, caused for example by variant AMYLD1 '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.
Sulfonation of the reactive cysteine Cys-30 enhances the stability of the native conformation of TTR, avoiding misassembly of the protein leading to amyloid formation.
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
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.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4.
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
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.
Sequence similarities
Belongs to the transthyretin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length147
- Mass (Da)15,887
- Last updated1987-03-20 v1
- Checksum3A6AEBCBBA56BC44
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A087WT59 | A0A087WT59_HUMAN | TTR | 115 | ||
A0A087WV45 | A0A087WV45_HUMAN | TTR | 23 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 41 | in Ref. 3; AAA98771 | ||||
Sequence: R → P | ||||||
Sequence conflict | 147 | in Ref. 12; CAG33189 | ||||
Sequence: E → D |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
K02091 EMBL· GenBank· DDBJ | AAA60011.1 EMBL· GenBank· DDBJ | mRNA | ||
M10605 EMBL· GenBank· DDBJ | AAA60012.1 EMBL· GenBank· DDBJ | mRNA | ||
M11518 EMBL· GenBank· DDBJ | AAA98771.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M11844 EMBL· GenBank· DDBJ | AAA60013.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X59498 EMBL· GenBank· DDBJ | CAA42087.1 EMBL· GenBank· DDBJ | mRNA | ||
D00096 EMBL· GenBank· DDBJ | BAA00059.1 EMBL· GenBank· DDBJ | mRNA | ||
M15517 EMBL· GenBank· DDBJ | AAA60018.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M15515 EMBL· GenBank· DDBJ | AAA60018.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M15516 EMBL· GenBank· DDBJ | AAA60018.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U19780 EMBL· GenBank· DDBJ | AAA73473.1 EMBL· GenBank· DDBJ | mRNA | ||
AF162690 EMBL· GenBank· DDBJ | AAD45014.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312051 EMBL· GenBank· DDBJ | BAG34987.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007189 EMBL· GenBank· DDBJ | AAP35853.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456908 EMBL· GenBank· DDBJ | CAG33189.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471088 EMBL· GenBank· DDBJ | EAX01264.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC005310 EMBL· GenBank· DDBJ | AAH05310.1 EMBL· GenBank· DDBJ | mRNA | ||
BC020791 EMBL· GenBank· DDBJ | AAH20791.1 EMBL· GenBank· DDBJ | mRNA | ||
S63185 EMBL· GenBank· DDBJ | AAD14937.2 EMBL· GenBank· DDBJ | Genomic DNA | ||
S72385 EMBL· GenBank· DDBJ | AAD14098.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M11714 EMBL· GenBank· DDBJ | AAA61181.1 EMBL· GenBank· DDBJ | mRNA | ||
M63285 EMBL· GenBank· DDBJ | AAA36784.1 EMBL· GenBank· DDBJ | Genomic DNA |