TTR

Protein identityUniProt · HPA

UniProt accession

P02766

Gene

TTR

Ensembl

ENSG00000118271

Chromosome

18

Canonical length

147 aa

Protein class

Cancer-related genes, Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Golgi apparatus

Secretome location

Secreted to blood

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes one of the three prealbumins, which include alpha-1-antitrypsin, transthyretin and orosomucoid. The encoded protein, transthyretin, is a homo-tetrameric carrier protein, which transports thyroid hormones in the plasma and cerebrospinal fluid. It is also involved in the transport of retinol (vitamin A) in the plasma by associating with retinol-binding protein. The protein may also be involved in other intracellular processes including proteolysis, nerve regeneration, autophagy and glucose homeostasis. Mutations in this gene are associated with amyloid deposition, predominantly affecting peripheral nerves or the heart, while a small percentage of the gene mutations are non-amyloidogenic. The mutations are implicated in the etiology of several diseases, including amyloidotic polyneuropathy, euthyroid hyperthyroxinaemia, amyloidotic vitreous opacities, cardiomyopathy, oculoleptomeningeal amyloidosis, meningocerebrovascular amyloidosis and carpal tunnel syndrome. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

147 residues, UniProt reviewed canonical sequence.

>P02766|TTR
     1  MASHRLLLLC LAGLVFVSEA GPTGTGESKC PLMVKVLDAV RGSPAINVAV HVFRKAADDT
    61  WEPFASGKTS ESGELHGLTT EEEFVEGIYK VEIDTKSYWK ALGISPFHEH AEVVFTANDS
   121  GPRRYTIAAL LSPYSYSTTA VVTNPKE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TTR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

672,505 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TTR.

Disease | AllUniProt

Conditions TTR is implicated in, by any mechanism.

• Amyloidosis, hereditary systemic 1 (AMYLD1) MIM:105210
• Hyperthyroxinemia, dystransthyretinemic (DTTRH) MIM:145680
• Carpal tunnel syndrome 1 (CTS1) MIM:115430

Disease | GeneticClinVar

134 pathogenic / likely-pathogenic of 437 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Amyloidosis, hereditary systemic 1
• Cardiovascular phenotype
• Hyperthyroxinemia, dystransthyretinemic
• Carpal tunnel syndrome 1
• Charcot-Marie-Tooth disease

Disease | ImmuneIEDB

Conditions an epitope on TTR was assayed in.

• hereditary systemic amyloidosis 1 B cell

ReferencesPubMed · IEDB

Publications for TTR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.76

gnomAD pLI

0.52

gnomAD missense Z

1.01

DepMap mean gene effect

0.08

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• negative regulation of glomerular filtration
• phototransduction, visible light
• purine nucleobase metabolic process
• retinoid metabolic process

Molecular functions

• hormone activity
• hormone binding
• identical protein binding
• molecular sequestering activity
• protein-containing complex binding

Cellular components

• azurophil granule lumen
• extracellular exosome
• extracellular region
• extracellular space
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• Transthyretin/hydroxyisourate hydrolase
• Transthyretin/hydroxyisourate hydrolase domain
• Transthyretin, thyroxine binding site
• Transthyretin, conserved site
• Transthyretin/hydroxyisourate hydrolase domain superfamily
• HIUase/Transthyretin family

KeywordsUniProt

• Amyloid
• Amyloidosis
• Cytoplasm
• Gamma-carboxyglutamic acid
• Glycoprotein
• Hormone
• Neuropathy
• Phosphoprotein
• Secreted
• Signal
• Sulfation
• Thyroid hormone
• Transport

InteractionsUniProt · HPA

Protein binding partners of TTR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• RBP4
• ATF4
• CHD3
• ELP1
• FEZ1
• MT3
• SETDB1
• VIM