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UniProtKB - P02766 (TTHY_HUMAN)
Protein
Transthyretin
Gene
TTR
Organism
Homo sapiens (Human)
Status
Functioni
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
1 PublicationMiscellaneous
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.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 35 | L-thyroxine | 1 | |
Binding sitei | 74 | L-thyroxine | 1 |
GO - Molecular functioni
- hormone activity Source: UniProtKB-KW
- identical protein binding Source: IntAct
- protein-containing complex binding Source: Ensembl
- thyroid hormone binding Source: GO_Central
GO - Biological processi
- purine nucleobase metabolic process Source: GO_Central
- retinol metabolic process Source: InterPro
- thyroid hormone transport Source: InterPro
Keywordsi
Molecular function | Hormone, Thyroid hormone |
Biological process | Transport |
Enzyme and pathway databases
PathwayCommonsi | P02766 |
Reactomei | R-HSA-2453864, Retinoid cycle disease events R-HSA-2453902, The canonical retinoid cycle in rods (twilight vision) R-HSA-3000171, Non-integrin membrane-ECM interactions R-HSA-6798695, Neutrophil degranulation R-HSA-975634, Retinoid metabolism and transport R-HSA-977225, Amyloid fiber formation |
SignaLinki | P02766 |
Names & Taxonomyi
Protein namesi | Recommended name: TransthyretinAlternative name(s): ATTR Prealbumin TBPA |
Gene namesi | Name:TTR Synonyms:PALB |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:12405, TTR |
MIMi | 176300, gene |
neXtProti | NX_P02766 |
VEuPathDBi | HostDB:ENSG00000118271 |
Subcellular locationi
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular region Source: Reactome
- extracellular space Source: UniProtKB
Lysosome
- azurophil granule lumen Source: Reactome
Other locations
- protein-containing complex Source: Ensembl
Keywords - Cellular componenti
Amyloid, Cytoplasm, SecretedPathology & Biotechi
Involvement in diseasei
Amyloidosis, transthyretin-related (AMYL-TTR)73 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_007547 | 30 | C → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918083EnsemblClinVar. | 1 | |
Natural variantiVAR_038959 | 32 | L → P in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs121918094EnsemblClinVar. | 1 | |
Natural variantiVAR_007548 | 38 | D → E in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_007549 | 38 | D → G in AMYL-TTR; leptomeningeal amyloidosis; leads to unfolding and exposure of N-118 to glycosylation by STT3B and subsequent degradation by the ERAD pathway. 2 PublicationsCorresponds to variant dbSNP:rs121918098EnsemblClinVar. | 1 | |
Natural variantiVAR_007550 | 40 | V → I in AMYL-TTR; late-onset amyloid polyneuropathy with carpal tunnel syndrome. 2 PublicationsCorresponds to variant dbSNP:rs121918093EnsemblClinVar. | 1 | |
Natural variantiVAR_038961 | 43 | S → N in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007551 | 44 | P → S in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs11541790EnsemblClinVar. | 1 | |
Natural variantiVAR_010658 | 48 | V → M in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007552 | 50 | V → A in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs79977247EnsemblClinVar. | 1 | |
Natural variantiVAR_038962 | 50 | V → G in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs79977247EnsemblClinVar. | 1 | |
Natural variantiVAR_007553 | 50 | V → L in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs28933979EnsemblClinVar. | 1 | |
Natural variantiVAR_007554 | 50 | V → M in AMYL-TTR; amyloid polyneuropathy; by far the most frequent mutation. 10 PublicationsCorresponds to variant dbSNP:rs28933979EnsemblClinVar. | 1 | |
Natural variantiVAR_007555 | 53 | F → I in AMYL-TTR; Jewish 'SKO' amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs121918068EnsemblClinVar. | 1 | |
Natural variantiVAR_007556 | 53 | F → L in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918068EnsemblClinVar. | 1 | |
Natural variantiVAR_038964 | 53 | F → V in AMYL-TTR; amyloid polyneuropathy. 4 Publications | 1 | |
Natural variantiVAR_038965 | 54 | R → T in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_038966 | 55 | K → N in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007557 | 56 | A → P in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918077EnsemblClinVar. | 1 | |
Natural variantiVAR_038967 | 58 | D → A in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_038968 | 58 | D → V in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_038969 | 61 | W → L in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_038970 | 62 | E → D in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs11541796EnsemblClinVar. | 1 | |
Natural variantiVAR_007558 | 62 | E → G in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs11541796EnsemblClinVar. | 1 | |
Natural variantiVAR_038971 | 64 | F → S in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs104894665EnsemblClinVar. | 1 | |
Natural variantiVAR_007559 | 65 | A → D in AMYL-TTR; amyloid cardiomyopathy. Corresponds to variant dbSNP:rs730881169EnsemblClinVar. | 1 | |
Natural variantiVAR_038972 | 65 | A → S in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007560 | 65 | A → T in AMYL-TTR; amyloid cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918078EnsemblClinVar. | 1 | |
Natural variantiVAR_007561 | 67 | G → A in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs121918090EnsemblClinVar. | 1 | |
Natural variantiVAR_038973 | 67 | G → E in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_007562 | 67 | G → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs387906523EnsemblClinVar. | 1 | |
Natural variantiVAR_007563 | 67 | G → V in AMYL-TTR; amyloid polyneuropathy with carpal tunnel syndrome. | 1 | |
Natural variantiVAR_007564 | 69 | T → A in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918081EnsemblClinVar. | 1 | |
Natural variantiVAR_038974 | 69 | T → I in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_007565 | 70 | S → I in AMYL-TTR; amyloid cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs121918080EnsemblClinVar. | 1 | |
Natural variantiVAR_007566 | 70 | S → R in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs386134269EnsemblClinVar. | 1 | |
Natural variantiVAR_007567 | 72 | S → P in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_038975 | 73 | G → E in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs121918097EnsemblClinVar. | 1 | |
Natural variantiVAR_007568 | 74 | E → G in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_038976 | 74 | E → K in AMYL-TTR; early-onset amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007569 | 75 | L → P in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918079EnsemblClinVar. | 1 | |
Natural variantiVAR_038977 | 75 | L → Q in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007570 | 78 | L → H in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918069EnsemblClinVar. | 1 | |
Natural variantiVAR_007571 | 78 | L → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918069EnsemblClinVar. | 1 | |
Natural variantiVAR_007572 | 79 | T → K in AMYL-TTR; amyloid cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs730881163EnsemblClinVar. | 1 | |
Natural variantiVAR_007573 | 80 | T → A in AMYL-TTR; amyloid polyneuropathy and cardiomyopathy. 4 PublicationsCorresponds to variant dbSNP:rs121918070EnsemblClinVar. | 1 | |
Natural variantiVAR_038978 | 81 | E → G in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007574 | 81 | E → K in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918086EnsemblClinVar. | 1 | |
Natural variantiVAR_007575 | 84 | F → L in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918091EnsemblClinVar. | 1 | |
Natural variantiVAR_007576 | 88 | I → L in AMYL-TTR; amyloid cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918085EnsemblClinVar. | 1 | |
Natural variantiVAR_007577 | 89 | Y → H in AMYL-TTR; leptomeningeal amyloidosis; vitreous amyloid in some patients. 1 PublicationCorresponds to variant dbSNP:rs121918100EnsemblClinVar. | 1 | |
Natural variantiVAR_007578 | 90 | K → N in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs267607160EnsemblClinVar. | 1 | |
Natural variantiVAR_007579 | 91 | V → A in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918084EnsemblClinVar. | 1 | |
Natural variantiVAR_007580 | 93 | I → V in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007582 | 97 | S → Y in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918071EnsemblClinVar. | 1 | |
Natural variantiVAR_038979 | 98 | Y → F in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs958191819EnsemblClinVar. | 1 | |
Natural variantiVAR_007583 | 104 | I → N in AMYL-TTR; vitrous amyloid. 1 Publication | 1 | |
Natural variantiVAR_007584 | 104 | I → S in AMYL-TTR; amyloid polyneuropathy; almost no RBP binding. 3 PublicationsCorresponds to variant dbSNP:rs121918072EnsemblClinVar. | 1 | |
Natural variantiVAR_038980 | 104 | I → T in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_010659 | 109 | E → K in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007585 | 109 | E → Q in AMYL-TTR; amyloid polyneuropathy and cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918082EnsemblClinVar. | 1 | |
Natural variantiVAR_007587 | 111 | A → S in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007588 | 117 | A → G in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918087EnsemblClinVar. | 1 | |
Natural variantiVAR_038982 | 117 | A → S in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs267607161EnsemblClinVar. | 1 | |
Natural variantiVAR_038984 | 126 | T → N in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs1456101911Ensembl. | 1 | |
Natural variantiVAR_038985 | 127 | I → M in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007592 | 127 | I → V in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918089EnsemblClinVar. | 1 | |
Natural variantiVAR_007594 | 131 | L → M in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs121918073EnsemblClinVar. | 1 | |
Natural variantiVAR_007595 | 134 | Y → C in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918075EnsemblClinVar. | 1 | |
Natural variantiVAR_007596 | 136 | Y → S in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs730881167EnsemblClinVar. | 1 | |
Natural variantiVAR_038986 | 140 | A → S in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs876658108EnsemblClinVar. | 1 | |
Natural variantiVAR_038987 | 142 | V → A in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007600 | 142 | V → I in AMYL-TTR. 3 PublicationsCorresponds to variant dbSNP:rs76992529EnsemblClinVar. | 1 | |
Natural variantiVAR_038988 | 144 | N → S in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs144965179EnsemblClinVar. | 1 |
Hyperthyroxinemia, dystransthyretinemic (DTTRH)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA condition characterized by elevation of total and free thyroxine in healthy, euthyroid persons without detectable binding protein abnormalities.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_007593 | 129 | A → T in DTTRH; increased affinity for thyroxine. 2 PublicationsCorresponds to variant dbSNP:rs267607159EnsemblClinVar. | 1 |
Carpal tunnel syndrome 1 (CTS1)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_007598 | 134 | Y → H in CTS1; amyloid deposit on carpal tunnel; patients show no other abnormalities. 1 PublicationCorresponds to variant dbSNP:rs121918088EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 107 | F → M: Loss of tetramerization; when associated with M-130. 1 Publication | 1 | |
Mutagenesisi | 130 | L → M: Loss of tetramerization; when associated with M-107. 1 Publication | 1 |
Keywords - Diseasei
Amyloidosis, Disease variant, NeuropathyOrganism-specific databases
DisGeNETi | 7276 |
GeneReviewsi | TTR |
MalaCardsi | TTR |
MIMi | 105210, phenotype 115430, phenotype 145680, phenotype |
OpenTargetsi | ENSG00000118271 |
Orphaneti | 85451, ATTRV122I amyloidosis 85447, ATTRV30M amyloidosis 597939, Euthyroid dysprealbuminemic hyperthyroxinemia |
PharmGKBi | PA37069 |
Miscellaneous databases
Pharosi | P02766, Tclin |
Chemistry databases
ChEMBLi | CHEMBL3194 |
DrugBanki | DB07201, (2S)-3-[(9H-fluoren-9-ylideneamino)oxy]-2-methylpropanoic acid DB07176, 1-Naphthylamine-5-sulfonic acid DB07047, 2',4'-DICHLORO-4-HYDROXY-1,1'-BIPHENYL-3-CARBOXYLIC ACID DB06935, 2',6'-DIFLUOROBIPHENYL-4-CARBOXYLIC ACID DB02417, 2,4,6-Tribromophenol DB07694, 2,5-dichloro-N-(3,5-dibromo-4-hydroxyphenyl)benzamide DB08101, 2,6-dibromo-4-[(E)-2-phenylethenyl]phenol DB08103, 2,6-dibromo-4-phenoxyphenol DB08100, 2,6-dimethyl-4-[(E)-2-phenylethenyl]phenol DB06907, 2-(2,6-DICHLOROPHENYL)-1,3-BENZOXAZOLE-6-CARBOXYLIC ACID DB08207, 2-(3,5-DIMETHYLPHENYL)-1,3-BENZOXAZOLE DB04756, 2-[(3,5-Dichloro-4-trioxidanylphenyl)amino]benzoic acid DB04674, 2-HYDROXY-3,5-DIIODOBENZOIC ACID DB07775, 3',5'-DIBROMO-2',4,4',6'-TETRAHYDROXY AURONE DB07753, 3',5'-DIFLUOROBIPHENYL-4-CARBOXYLIC ACID DB03239, 3',5'-Dinitro-N-Acetyl-L-Thyronine DB03346, 3,3',5,5'-tetrachlorobiphenyl-4,4'-diol DB08102, 3,5-dibromobiphenyl-4-ol DB07282, 3-({[(1Z)-(2-methoxyphenyl)methylidene]amino}oxy)propanoic acid DB07240, 3-[(9H-fluoren-9-ylideneamino)oxy]propanoic acid DB06885, 3-[({(1E)-[2-(trifluoromethyl)phenyl]methylidene}amino)oxy]propanoic acid DB08206, 4-(1,3-BENZOXAZOL-2-YL)-2,6-DIBROMOPHENOL DB08205, 4-(1,3-BENZOXAZOL-2-YL)-2,6-DIMETHYLPHENOL DB01838, 6,4'-Dihydroxy-3-Methyl-3',5'-Dibromoflavone DB04474, 8-anilinonaphthalene-1-sulfonic acid DB09130, Copper DB03682, Dibenzofuran-4,6-Dicarboxylic Acid DB00586, Diclofenac DB00255, Diethylstilbestrol DB00861, Diflunisal DB01093, Dimethyl sulfoxide DB02266, Flufenamic acid DB05352, Fx-1006A DB01645, Genistein DB00451, Levothyroxine DB00279, Liothyronine DB01583, Liotrix DB07962, METHYL N-[(2',4'-DIFLUORO-4-HYDROXY-5-IODOBIPHENYL-3-YL)CARBONYL]-BETA-ALANINATE DB07693, N-(3,5-dibromo-4-hydroxyphenyl)-2,6-dimethylbenzamide DB07695, N-(3,5-dibromo-4-hydroxyphenyl)-4-hydroxy-3,5-dimethylbenzamide DB08104, N-(3,5-dibromo-4-hydroxyphenyl)benzamide DB02698, N-(M-Trifluoromethylphenyl) Phenoxazine-4,6-Dicarboxylic Acid DB07963, N-[(2',4'-DIFLUORO-4-HYDROXY-5-IODOBIPHENYL-3-YL)CARBONYL]-BETA-ALANINE DB05235, NRP409 DB02179, O-Trifluoromethylphenyl Anthranilic Acid DB03167, Pentabromophenol DB02709, Resveratrol DB11644, Tafamidis DB01751, Tetraiodothyroacetic acid DB09100, Thyroid, porcine DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
DrugCentrali | P02766 |
GuidetoPHARMACOLOGYi | 2851 |
Genetic variation databases
BioMutai | TTR |
DMDMi | 136464 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | 6 PublicationsAdd BLAST | 20 | |
ChainiPRO_0000035755 | 21 – 147 | TransthyretinAdd BLAST | 127 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 62 | 4-carboxyglutamate; in a patient with Moyamoya disease1 Publication | 1 | |
Modified residuei | 72 | PhosphoserineBy similarity | 1 | |
Glycosylationi | 118 | N-linked (GlcNAc...) asparagine2 Publications | 1 |
Post-translational modificationi
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.3 Publications
Keywords - PTMi
Gamma-carboxyglutamic acid, Glycoprotein, PhosphoproteinProteomic databases
CPTACi | non-CPTAC-1165 |
EPDi | P02766 |
jPOSTi | P02766 |
MassIVEi | P02766 |
MaxQBi | P02766 |
PaxDbi | P02766 |
PeptideAtlasi | P02766 |
PRIDEi | P02766 |
ProteomicsDBi | 51586 |
TopDownProteomicsi | P02766 |
2D gel databases
DOSAC-COBS-2DPAGEi | P02766 |
REPRODUCTION-2DPAGEi | P02766 |
SWISS-2DPAGEi | P02766 |
UCD-2DPAGEi | P02766 |
PTM databases
CarbonylDBi | P02766 |
GlyGeni | P02766, 1 site |
iPTMneti | P02766 |
PhosphoSitePlusi | P02766 |
Expressioni
Tissue specificityi
Detected in serum and cerebrospinal fluid (at protein level). Highly expressed in choroid plexus epithelial cells. Detected in retina pigment epithelium and liver.2 Publications
Gene expression databases
Bgeei | ENSG00000118271, Expressed in pigmented layer of retina and 148 other tissues |
ExpressionAtlasi | P02766, baseline and differential |
Genevisiblei | P02766, HS |
Organism-specific databases
HPAi | ENSG00000118271, Tissue enriched (choroid) |
Interactioni
Subunit structurei
Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules.
Interacts with RBP4.
13 PublicationsBinary interactionsi
P02766
GO - Molecular functioni
- hormone activity Source: UniProtKB-KW
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 113127, 98 interactors |
CORUMi | P02766 |
DIPi | DIP-1083N |
IntActi | P02766, 102 interactors |
MINTi | P02766 |
STRINGi | 9606.ENSP00000237014 |
Chemistry databases
BindingDBi | P02766 |
Miscellaneous databases
RNActi | P02766, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
AlphaFoldDBi | P02766 |
BMRBi | P02766 |
PCDDBi | P02766 |
SMRi | P02766 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P02766 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 135 – 139 | L-thyroxine binding | 5 |
Domaini
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 similaritiesi
Belongs to the transthyretin family.Curated
Keywords - Domaini
SignalPhylogenomic databases
eggNOGi | KOG3006, Eukaryota |
GeneTreei | ENSGT01040000240588 |
HOGENOMi | CLU_115536_2_0_1 |
InParanoidi | P02766 |
OMAi | TWEPFAT |
OrthoDBi | 720138at2759 |
PhylomeDBi | P02766 |
TreeFami | TF300210 |
Family and domain databases
Gene3Di | 2.60.40.180, 1 hit |
InterProi | View protein in InterPro IPR023418, Thyroxine_BS IPR030178, Transthyretin IPR000895, Transthyretin/HIU_hydrolase IPR023416, Transthyretin/HIU_hydrolase_d IPR036817, Transthyretin/HIU_hydrolase_sf IPR023419, Transthyretin_CS |
PANTHERi | PTHR10395, PTHR10395, 1 hit PTHR10395:SF12, PTHR10395:SF12, 1 hit |
Pfami | View protein in Pfam PF00576, Transthyretin, 1 hit |
PRINTSi | PR00189, TRNSTHYRETIN |
SMARTi | View protein in SMART SM00095, TR_THY, 1 hit |
SUPFAMi | SSF49472, SSF49472, 1 hit |
PROSITEi | View protein in PROSITE PS00768, TRANSTHYRETIN_1, 1 hit PS00769, TRANSTHYRETIN_2, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
P02766-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV
60 70 80 90 100
HVFRKAADDT WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK
110 120 130 140
ALGISPFHEH AEVVFTANDS GPRRYTIAAL LSPYSYSTTA VVTNPKE
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A087WT59 | A0A087WT59_HUMAN | Transthyretin | TTR | 115 | Annotation score: | ||
A0A087WV45 | A0A087WV45_HUMAN | Transthyretin | TTR | 23 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 41 | R → P in AAA98771 (PubMed:4054629).Curated | 1 | |
Sequence conflicti | 147 | E → D in CAG33189 (Ref. 12) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_007546 | 26 | G → S5 PublicationsCorresponds to variant dbSNP:rs1800458EnsemblClinVar. | 1 | |
Natural variantiVAR_007547 | 30 | C → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918083EnsemblClinVar. | 1 | |
Natural variantiVAR_038959 | 32 | L → P in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs121918094EnsemblClinVar. | 1 | |
Natural variantiVAR_038960 | 33 | M → I1 Publication | 1 | |
Natural variantiVAR_007548 | 38 | D → E in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_007549 | 38 | D → G in AMYL-TTR; leptomeningeal amyloidosis; leads to unfolding and exposure of N-118 to glycosylation by STT3B and subsequent degradation by the ERAD pathway. 2 PublicationsCorresponds to variant dbSNP:rs121918098EnsemblClinVar. | 1 | |
Natural variantiVAR_007550 | 40 | V → I in AMYL-TTR; late-onset amyloid polyneuropathy with carpal tunnel syndrome. 2 PublicationsCorresponds to variant dbSNP:rs121918093EnsemblClinVar. | 1 | |
Natural variantiVAR_038961 | 43 | S → N in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007551 | 44 | P → S in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs11541790EnsemblClinVar. | 1 | |
Natural variantiVAR_010658 | 48 | V → M in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007552 | 50 | V → A in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs79977247EnsemblClinVar. | 1 | |
Natural variantiVAR_038962 | 50 | V → G in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs79977247EnsemblClinVar. | 1 | |
Natural variantiVAR_007553 | 50 | V → L in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs28933979EnsemblClinVar. | 1 | |
Natural variantiVAR_007554 | 50 | V → M in AMYL-TTR; amyloid polyneuropathy; by far the most frequent mutation. 10 PublicationsCorresponds to variant dbSNP:rs28933979EnsemblClinVar. | 1 | |
Natural variantiVAR_038963 | 53 | F → C in a patient with amyloidosis. 2 Publications | 1 | |
Natural variantiVAR_007555 | 53 | F → I in AMYL-TTR; Jewish 'SKO' amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs121918068EnsemblClinVar. | 1 | |
Natural variantiVAR_007556 | 53 | F → L in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918068EnsemblClinVar. | 1 | |
Natural variantiVAR_038964 | 53 | F → V in AMYL-TTR; amyloid polyneuropathy. 4 Publications | 1 | |
Natural variantiVAR_038965 | 54 | R → T in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_038966 | 55 | K → N in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007557 | 56 | A → P in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918077EnsemblClinVar. | 1 | |
Natural variantiVAR_038967 | 58 | D → A in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_038968 | 58 | D → V in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_038969 | 61 | W → L in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_038970 | 62 | E → D in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs11541796EnsemblClinVar. | 1 | |
Natural variantiVAR_007558 | 62 | E → G in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs11541796EnsemblClinVar. | 1 | |
Natural variantiVAR_038971 | 64 | F → S in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs104894665EnsemblClinVar. | 1 | |
Natural variantiVAR_007559 | 65 | A → D in AMYL-TTR; amyloid cardiomyopathy. Corresponds to variant dbSNP:rs730881169EnsemblClinVar. | 1 | |
Natural variantiVAR_038972 | 65 | A → S in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007560 | 65 | A → T in AMYL-TTR; amyloid cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918078EnsemblClinVar. | 1 | |
Natural variantiVAR_007561 | 67 | G → A in AMYL-TTR; amyloid polyneuropathy. 2 PublicationsCorresponds to variant dbSNP:rs121918090EnsemblClinVar. | 1 | |
Natural variantiVAR_038973 | 67 | G → E in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_007562 | 67 | G → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs387906523EnsemblClinVar. | 1 | |
Natural variantiVAR_007563 | 67 | G → V in AMYL-TTR; amyloid polyneuropathy with carpal tunnel syndrome. | 1 | |
Natural variantiVAR_007564 | 69 | T → A in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918081EnsemblClinVar. | 1 | |
Natural variantiVAR_038974 | 69 | T → I in AMYL-TTR. 2 Publications | 1 | |
Natural variantiVAR_007565 | 70 | S → I in AMYL-TTR; amyloid cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs121918080EnsemblClinVar. | 1 | |
Natural variantiVAR_007566 | 70 | S → R in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs386134269EnsemblClinVar. | 1 | |
Natural variantiVAR_007567 | 72 | S → P in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_038975 | 73 | G → E in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs121918097EnsemblClinVar. | 1 | |
Natural variantiVAR_007568 | 74 | E → G in AMYL-TTR; amyloid polyneuropathy. | 1 | |
Natural variantiVAR_038976 | 74 | E → K in AMYL-TTR; early-onset amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007569 | 75 | L → P in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918079EnsemblClinVar. | 1 | |
Natural variantiVAR_038977 | 75 | L → Q in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007570 | 78 | L → H in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918069EnsemblClinVar. | 1 | |
Natural variantiVAR_007571 | 78 | L → R in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918069EnsemblClinVar. | 1 | |
Natural variantiVAR_007572 | 79 | T → K in AMYL-TTR; amyloid cardiomyopathy. 1 PublicationCorresponds to variant dbSNP:rs730881163EnsemblClinVar. | 1 | |
Natural variantiVAR_007573 | 80 | T → A in AMYL-TTR; amyloid polyneuropathy and cardiomyopathy. 4 PublicationsCorresponds to variant dbSNP:rs121918070EnsemblClinVar. | 1 | |
Natural variantiVAR_038978 | 81 | E → G in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_007574 | 81 | E → K in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs121918086EnsemblClinVar. | 1 | |
Natural variantiVAR_007575 | 84 | F → L in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918091EnsemblClinVar. | 1 | |
Natural variantiVAR_007576 | 88 | I → L in AMYL-TTR; amyloid cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918085EnsemblClinVar. | 1 | |
Natural variantiVAR_007577 | 89 | Y → H in AMYL-TTR; leptomeningeal amyloidosis; vitreous amyloid in some patients. 1 PublicationCorresponds to variant dbSNP:rs121918100EnsemblClinVar. | 1 | |
Natural variantiVAR_007578 | 90 | K → N in AMYL-TTR; amyloid polyneuropathy. 1 PublicationCorresponds to variant dbSNP:rs267607160EnsemblClinVar. | 1 | |
Natural variantiVAR_007579 | 91 | V → A in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918084EnsemblClinVar. | 1 | |
Natural variantiVAR_007580 | 93 | I → V in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007581 | 94 | D → H. Corresponds to variant dbSNP:rs730881164EnsemblClinVar. | 1 | |
Natural variantiVAR_007582 | 97 | S → Y in AMYL-TTR; amyloid polyneuropathy. 4 PublicationsCorresponds to variant dbSNP:rs121918071EnsemblClinVar. | 1 | |
Natural variantiVAR_038979 | 98 | Y → F in AMYL-TTR. 2 PublicationsCorresponds to variant dbSNP:rs958191819EnsemblClinVar. | 1 | |
Natural variantiVAR_007583 | 104 | I → N in AMYL-TTR; vitrous amyloid. 1 Publication | 1 | |
Natural variantiVAR_007584 | 104 | I → S in AMYL-TTR; amyloid polyneuropathy; almost no RBP binding. 3 PublicationsCorresponds to variant dbSNP:rs121918072EnsemblClinVar. | 1 | |
Natural variantiVAR_038980 | 104 | I → T in AMYL-TTR. 1 Publication | 1 | |
Natural variantiVAR_010659 | 109 | E → K in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_007585 | 109 | E → Q in AMYL-TTR; amyloid polyneuropathy and cardiomyopathy. 2 PublicationsCorresponds to variant dbSNP:rs121918082EnsemblClinVar. | 1 | |
Natural variantiVAR_007586 | 110 | H → N2 PublicationsCorresponds to variant dbSNP:rs121918074EnsemblClinVar. | 1 | |
Natural variantiVAR_007587 | 111 | A → S in AMYL-TTR; amyloid polyneuropathy. 1 Publication | 1 | |
Natural variantiVAR_038981 | 114 | V → A in a patient with amyloidosis. 2 Publications | 1 | |
Natural variantiVAR_007588 | 117 | A → G in AMYL-TTR; amyloid polyneuropathy. 3 PublicationsCorresponds to variant dbSNP:rs121918087EnsemblClinVar. | 1 | |
Natural variantiVAR_038982 | 117 | A → S in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs267607161EnsemblClinVar. | 1 | |
Natural variantiVAR_007589 | 121 | G → S2 PublicationsCorresponds to variant dbSNP:rs755337715EnsemblClinVar. | 1 | |
Natural variantiVAR_007590 | 122 | P → R. | 1 | |
Natural variantiVAR_007591 | 124 | R → C. Corresponds to variant dbSNP:rs745834030EnsemblClinVar. | 1 | |
Natural variantiVAR_038983 | 124 | R → H2 PublicationsCorresponds to variant dbSNP:rs121918095EnsemblClinVar. | 1 | |
Natural variantiVAR_038984 | 126 | T → N in AMYL-TTR. 1 PublicationCorresponds to variant dbSNP:rs1456101911Ensembl. | 1 | |
Natural variantiVAR_038985 | 127 | I → M in AMYL-TTR. 1 Publication |