transthyretin | Carrier proteins | IUPHAR/BPS Guide to PHARMACOLOGY

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transthyretin

Target not currently curated in GtoImmuPdb

Target id: 2851

Nomenclature: transthyretin

Abbreviated Name: TTR

Family: Carrier proteins

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 147 18q12.1 TTR transthyretin
Mouse - 147 18 A2 Ttr transthyretin
Rat - 147 18p Ttr transthyretin
Previous and Unofficial Names
carpal tunnel syndrome 1 [5] | CTS1 | PALB | prealbumin, amyloidosis type I
Database Links
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of wild-type TTR in complex with tafamidis.
PDB Id:  3TCT
Ligand:  tafamidis
Resolution:  1.3Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  The Structure of V122I Mutant Transthyretin in Complex with Tafamidis
PDB Id:  4HIS
Ligand:  tafamidis
Resolution:  1.2Å
Species:  Human
References:  6
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
tafamidis Hs Binding 8.7 pKd 2
pKd 8.7 (Kd 2x10-9 M) [2]
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Clinically-Relevant Mutations and Pathophysiology
Disease:  Familial amyloid cardiomyopathy
Description: Familial amyloid cardiomyopathy (FAP) is a degenerative disease caused by the formation of transthyretin (TTR) amyloidogenic fibrils in the heart.
Synonyms: Transthyretin amyloid cardiopathy
Transthyretin amyloidosis [Disease Ontology: DOID:0050638]
Transthyretin-related familial amyloid cardiomyopathy [Orphanet: ORPHA85451]
TTR-related cardiac amyloidosis
Disease Ontology: DOID:0050638
OMIM: 105210
Orphanet: ORPHA85451
Drugs: 
References:  2
Click column headers to sort
Type Species Amino acid change Nucleotide change Description Reference
Missense Human V30M 148G>A 1
Missense Human V122I 6
Gene Expression and Pathophysiology Comments
Excess production and accumulation of transthyretin (TTR) causes hereditary transthyretin-mediated amyloidosis. Two novel drugs are now approved to combat this disease: inotersen (Tegsedi®) [4] and patisiran (Onpattro®) [3]. Both of these drugs act to reduce the amount of TTR protein (both wild type and mutant) produced in the liver, but by slightly different mechanisms. Inotersen is an antisense oligonucleotide inhibitor of TTR synthesis, whereas patisiran is a double-stranded small interfering RNA (which targets a conserved sequence in the 3' UTR of mutant and wild-type TTR mRNA). Inotersen is administered subcutaneously, and patisiran is delivered by intravenous infusion in a lipid nanoparticle formulation.

References

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1. Benson MD. (1991) Inherited amyloidosis. J. Med. Genet., 28 (2): 73-8. [PMID:1848299]

2. Bulawa CE, Connelly S, Devit M, Wang L, Weigel C, Fleming JA, Packman J, Powers ET, Wiseman RL, Foss TR et al.. (2012) Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc. Natl. Acad. Sci. U.S.A., 109 (24): 9629-34. [PMID:22645360]

3. Hoy SM. (2018) Patisiran: First Global Approval. Drugs, 78 (15): 1625-1631. [PMID:30251172]

4. Keam SJ. (2018) Inotersen: First Global Approval. Drugs, 78 (13): 1371-1376. [PMID:30120737]

5. Murakami T, Tachibana S, Endo Y, Kawai R, Hara M, Tanase S, Ando M. (1994) Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant. Neurology, 44 (2): 315-8. [PMID:8309582]

6. Penchala SC, Connelly S, Wang Y, Park MS, Zhao L, Baranczak A, Rappley I, Vogel H, Liedtke M, Witteles RM et al.. (2013) AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin. Proc. Natl. Acad. Sci. U.S.A., 110 (24): 9992-7. [PMID:23716704]

How to cite this page

Carrier proteins: transthyretin. Last modified on 09/07/2019. Accessed on 05/04/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2851.