Transthyretin (TTR)

TBPA; PA; PLB; ATTR; PALB; Prealbumin; Prealbumin Amyloidosis Type I; Transports Thyroxine and Retinol

SPN	W086
HGNC	12405
MGI	98865
PubMed	7946531
RGD	3916
UniProt	P02766
Wiki	Transthyretin

TTR was originally called prealbumin because it ran faster than albumins on electrophoresis gels.Prealbumin is produced by the choroid plexus, by pancreatic islet cells in the embryonic yolk sac, and by enterochromaffin cells in the gastrointestinal mucosa, but the liver is quantitatively the most important source.9 Liver production is maintained until late in liver disease. Hydration status does not affect prealbumin levels. A negative acute phase reactant, the prealbumin level will transiently decrease in the presence of inflammation and in the immediate postsurgical period. Serum levels also decline in patients with conditions associated with protein malnutrition, such as malignancy, cirrhosis, protein-losing enteropathy, and zinc deficiency.

Reference

"Cloning and sequence analysis of cDNA for human prealbumin."
Biochem. Biophys. Res. Commun. 124:558-564(1984) [PubMed] [Europe PMC] [Abstract]

"Localization of the human prealbumin gene to chromosome 18."
Biochem. Biophys. Res. Commun. 129:753-758(1985) [PubMed] [Europe PMC] [Abstract]

"Structure of the chromosomal gene for human serum prealbumin."
Gene 37:191-197(1985) [PubMed] [Europe PMC] [Abstract]

"Structure of the human prealbumin gene."
J. Biol. Chem. 260:12224-12227(1985) [PubMed] [Europe PMC] [Abstract]

"Analyses of prealbumin mRNAs in individuals with familial amyloidotic polyneuropathy."
J. Biochem. 100:1215-1222(1986) [PubMed] [Europe PMC] [Abstract]

"Structure and expression of the mutant prealbumin gene associated with familial amyloidotic polyneuropathy."
Mol. Biol. Med. 3:329-338(1986) [PubMed] [Europe PMC] [Abstract]

"The transthyretin cDNA sequence is normal in transthyretin-derived senile systemic amyloidosis."
FEBS Lett. 281:177-180(1991) [PubMed] [Europe PMC] [Abstract]

"Transthyretin (prealbumin) gene in human primary hepatic cancer."
Sci. China, Ser. B, Chem. Life Sci. Earth Sci. 34:1312-1318(1991) [PubMed] [Europe PMC] [Abstract]

"Transthyretin localization in cultured and native human retinal pigment epithelium."
Exp. Eye Res. 68:629-636(1999) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"The amino acid sequence of human plasma prealbumin."
J. Biol. Chem. 249:6796-6805(1974) [PubMed] [Europe PMC] [Abstract]

"Primary structure of an amyloid prealbumin variant in familial polyneuropathy of Jewish origin."
Proc. Natl. Acad. Sci. U.S.A. 80:539-542(1983) [PubMed] [Europe PMC] [Abstract]

"Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type)."
Biochem. Biophys. Res. Commun. 116:880-888(1983) [PubMed] [Europe PMC] [Abstract]

"Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin."
Proc. Natl. Acad. Sci. U.S.A. 81:694-698(1984) [PubMed] [Europe PMC] [Abstract]

"Evidence that the amyloid fibril protein in senile systemic amyloidosis is derived from normal prealbumin."
Biochem. Biophys. Res. Commun. 154:648-653(1988) [PubMed] [Europe PMC] [Abstract]

"Characterization of a transthyretin-related amyloid fibril protein from cerebral amyloid angiopathy in type I familial amyloid polyneuropathy."
J. Neurol. Sci. 108:178-183(1992) [PubMed] [Europe PMC] [Abstract]

"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Nat. Biotechnol. 21:566-569(2003) [PubMed] [Europe PMC] [Abstract]

"A second transthyretin mutation at position 33 (Leu/Phe) associated with familial amyloidotic polyneuropathy."
Biochim. Biophys. Acta 1097:183-186(1991) [PubMed] [Europe PMC] [Abstract]

"Two transthyretin mutations (Glu42Gly, His90Asn) in an Italian family with amyloidosis."
Clin. Genet. 45:281-284(1994) [PubMed] [Europe PMC] [Abstract]

"Demonstration of transthyretin mRNA in the brain and other extrahepatic tissues in the rat."
J. Biol. Chem. 260:11793-11798(1985) [PubMed] [Europe PMC] [Abstract]

, Submitted (DEC-2008) to UniProtKB

"A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia."
J. Clin. Invest. 86:2025-2033(1990) [PubMed] [Europe PMC] [Abstract]

"Amyloid fibril composition and transthyretin gene structure in senile systemic amyloidosis."
Lab. Invest. 73:703-708(1995) [PubMed] [Europe PMC] [Abstract]

"Protein-DNA and protein-hormone interactions in prealbumin: a model of the thyroid hormone nuclear receptor?"
Nature 268:115-120(1977) [PubMed] [Europe PMC] [Abstract]

"Transthyretin: a choroid plexus-specific transport protein in human brain. The 1986 S. Weir Mitchell award."
Neurology 36:900-911(1986) [PubMed] [Europe PMC] [Abstract]

"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]

"Detection of a gamma-carboxy-glutamate as novel post-translational modification of human transthyretin."
Protein Pept. Lett. 15:43-46(2008) [PubMed] [Europe PMC] [Abstract]

"Cotranslational and posttranslational N-glycosylation of polypeptides by distinct mammalian OST isoforms."
Cell 136:272-283(2009) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Structure of human plasma prealbumin at 2.5-A resolution. A preliminary report on the polypeptide chain conformation, quaternary structure and thyroxine binding."
J. Mol. Biol. 88:1-12(1974) [PubMed] [Europe PMC] [Abstract]

"Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A."
J. Mol. Biol. 121:339-356(1978) [PubMed] [Europe PMC] [Abstract]

"Structure of Met30 variant of transthyretin and its amyloidogenic implications."
EMBO J. 12:735-741(1993) [PubMed] [Europe PMC] [Abstract]

"The X-ray crystal structure refinements of normal human transthyretin and the amyloidogenic Val-30-->Met variant to 1.7-A resolution."
J. Biol. Chem. 268:2416-2424(1993) [PubMed] [Europe PMC] [Abstract]

"Structure of a complex of two plasma proteins: transthyretin and retinol-binding protein."
Science 268:1039-1041(1995) [PubMed] [Europe PMC] [Abstract]

"Tertiary structures of amyloidogenic and non-amyloidogenic transthyretin variants: new model for amyloid fibril formation."
Amyloid 5:175-187(1998) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of amyloidogenic Leu55 --> Pro transthyretin variant reveals a possible pathway for transthyretin polymerization into amyloid fibrils."
J. Biol. Chem. 273:24715-24722(1998) [PubMed] [Europe PMC] [Abstract]

"Inhibiting transthyretin conformational changes that lead to amyloid fibril formation."
Proc. Natl. Acad. Sci. U.S.A. 95:12956-12960(1998) [PubMed] [Europe PMC] [Abstract]

"The structure of human retinol-binding protein (RBP) with its carrier protein transthyretin reveals an interaction with the carboxy terminus of RBP."
Biochemistry 38:2647-2653(1999) [PubMed] [Europe PMC] [Abstract]

"A comparative analysis of 23 structures of the amyloidogenic protein transthyretin."
J. Mol. Biol. 302:649-669(2000) [PubMed] [Europe PMC] [Abstract]

"Rational design of potent human transthyretin amyloid disease inhibitors."
Nat. Struct. Biol. 7:312-321(2000) [PubMed] [Europe PMC] [Abstract]

"An engineered transthyretin monomer that is nonamyloidogenic, unless it is partially denatured."
Biochemistry 40:11442-11452(2001) [PubMed] [Europe PMC] [Abstract]

"Transthyretin stability as a key factor in amyloidogenesis: X-ray analysis at atomic resolution."
J. Mol. Biol. 306:733-744(2001) [PubMed] [Europe PMC] [Abstract]

"Disulfide-bond formation in the transthyretin mutant Y114C prevents amyloid fibril formation in vivo and in vitro."
Biochemistry 41:13143-13151(2002) [PubMed] [Europe PMC] [Abstract]

"Benzoxazoles as transthyretin amyloid fibril inhibitors: synthesis, evaluation, and mechanism of action."
Angew. Chem. Int. Ed. 42:2758-2761(2003) [PubMed] [Europe PMC] [Abstract]

"Synthesis and characterization of potent bivalent amyloidosis inhibitors that bind prior to transthyretin tetramerization."
J. Am. Chem. Soc. 125:13404-13414(2003) [PubMed] [Europe PMC] [Abstract]

"Diflunisal analogues stabilize the native state of transthyretin. Potent inhibition of amyloidogenesis."
J. Med. Chem. 47:355-374(2004) [PubMed] [Europe PMC] [Abstract]

"X-ray crystallographic studies of two transthyretin variants: further insights into amyloidogenesis."
Acta Crystallogr. D 61:333-339(2005) [PubMed] [Europe PMC] [Abstract]

"The effect of iodide and chloride on transthyretin structure and stability."
Biochemistry 44:9290-9299(2005) [PubMed] [Europe PMC] [Abstract]

"Cys114-linked dimers of transthyretin are compatible with amyloid formation."
Biochemistry 44:13063-13070(2005) [PubMed] [Europe PMC] [Abstract]

"Kinetic stabilization of an oligomeric protein by a single ligand binding event."
J. Am. Chem. Soc. 127:5540-5551(2005) [PubMed] [Europe PMC] [Abstract]

"Kinetic stabilization of the native state by protein engineering: implications for inhibition of transthyretin amyloidogenesis."
J. Mol. Biol. 347:841-854(2005) [PubMed] [Europe PMC] [Abstract]

"The binding of 2,4-dinitrophenol to wild-type and amyloidogenic transthyretin."
Acta Crystallogr. D 62:512-519(2006) [PubMed] [Europe PMC] [Abstract]

"Structural basis for the protective role of sulfite against transthyretin amyloid formation."
Biochim. Biophys. Acta 1774:59-64(2007) [PubMed] [Europe PMC] [Abstract]

"Acidic pH-induced conformational changes in amyloidogenic mutant transthyretin."
J. Mol. Biol. 366:711-719(2007) [PubMed] [Europe PMC] [Abstract]

"Iodination of salicylic acid improves its binding to transthyretin."
Biochim. Biophys. Acta 1784:512-517(2008) [PubMed] [Europe PMC] [Abstract]

"Structural and mutational analyses of protein-protein interactions between transthyretin and retinol-binding protein."
FEBS J. 275:5841-5854(2008) [PubMed] [Europe PMC] [Abstract]

"Biochemical and structural evaluation of highly selective 2-arylbenzoxazole-based transthyretin amyloidogenesis inhibitors."
J. Med. Chem. 51:260-270(2008) [PubMed] [Europe PMC] [Abstract]

"Toward optimization of the linker substructure common to transthyretin amyloidogenesis inhibitors using biochemical and structural studies."
J. Med. Chem. 51:6348-6358(2008) [PubMed] [Europe PMC] [Abstract]

"Structural insight into pH-induced conformational changes within the native human transthyretin tetramer."
J. Mol. Biol. 382:1157-1167(2008) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of the F87M/L110M mutant of human transthyretin at pH 4.6 soaked."
Submitted (JUL-2008) to the PDB data bank

"Transthyretin mutations in health and disease."
Hum. Mutat. 5:191-196(1995) [PubMed] [Europe PMC] [Abstract]

"Revised analysis of amino acid replacement in a prealbumin variant (SKO-III) associated with familial amyloidotic polyneuropathy of Jewish origin."
Biochem. Biophys. Res. Commun. 123:921-928(1984) [PubMed] [Europe PMC] [Abstract]

"Biochemical and molecular genetic characterization of a new variant prealbumin associated with hereditary amyloidosis."
J. Clin. Invest. 78:6-12(1986) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of a human transthyretin variant."
Biochem. Biophys. Res. Commun. 148:471-477(1987) [PubMed] [Europe PMC] [Abstract]

"Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis."
J. Clin. Invest. 81:189-193(1988) [PubMed] [Europe PMC] [Abstract]

"A novel variant of transthyretin (Tyr114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases."
Biochem. Biophys. Res. Commun. 169:143-147(1990) [PubMed] [Europe PMC] [Abstract]

"Two novel variants of transthyretin identified in Japanese cases with familial amyloidotic polyneuropathy: transthyretin (Glu42 to Gly) and transthyretin (Ser50 to Arg)."
Biochem. Biophys. Res. Commun. 169:1117-1121(1990) [PubMed] [Europe PMC] [Abstract]

"Biochemical and clinical characterization of prealbuminCHICAGO: an apparently benign variant of serum prealbumin (transthyretin) discovered with high-resolution two-dimensional electrophoresis."
Am. J. Med. Genet. 39:442-452(1991) [PubMed] [Europe PMC] [Abstract]

"New mutant gene (transthyretin Arg 58) in cases with hereditary polyneuropathy detected by non-isotope method of single-strand conformation polymorphism analysis."
Biochem. Biophys. Res. Commun. 180:380-385(1991) [PubMed] [Europe PMC] [Abstract]

"A new transthyretin variant from a patient with familial amyloidotic polyneuropathy has asparagine substituted for histidine at position 90."
Clin. Genet. 39:6-12(1991) [PubMed] [Europe PMC] [Abstract]

"Two-tiered DNA-based diagnosis of transthyretin amyloidosis reveals two novel point mutations."
Neurology 41:893-898(1991) [PubMed] [Europe PMC] [Abstract]

"A new transthyretin mutation associated with amyloid cardiomyopathy."
Am. J. Hum. Genet. 50:1027-1030(1992) [PubMed] [Europe PMC] [Abstract]

"A novel transthyretin mutation associated with familial amyloidotic polyneuropathy."
Biochem. Biophys. Res. Commun. 182:520-526(1992) [PubMed] [Europe PMC] [Abstract]

"A novel transthyretin mutation at position 30 (Leu for Val) associated with familial amyloidotic polyneuropathy."
Biochem. Biophys. Res. Commun. 187:397-403(1992) [PubMed] [Europe PMC] [Abstract]

"Novel variant transthyretin gene (Ser50 to Ile) in familial cardiac amyloidosis."
Biochem. Biophys. Res. Commun. 187:460-466(1992) [PubMed] [Europe PMC] [Abstract]

"Familial amyloidotic polyneuropathy: a new transthyretin position 30 mutation (alanine for valine) in a family of German descent."
Clin. Genet. 41:70-73(1992) [PubMed] [Europe PMC] [Abstract]

"Transthyretin Pro55, a variant associated with early-onset, aggressive, diffuse amyloidosis with cardiac and neurologic involvement."
Hum. Genet. 89:353-356(1992) [PubMed] [Europe PMC] [Abstract]

"Two transthyretin variants (TTR Ala-49 and TTR Gln-89) in two Sicilian kindreds with hereditary amyloidosis."
Hum. Mutat. 1:211-215(1992) [PubMed] [Europe PMC] [Abstract]

"A new mutant transthyretin (Arg 10) associated with familial amyloid polyneuropathy."
J. Med. Genet. 29:888-891(1992) [PubMed] [Europe PMC] [Abstract]

"Familial amyloidotic polyneuropathy presenting with carpal tunnel syndrome and a new transthyretin mutation, asparagine 70."
Neurology 42:2094-2102(1992) [PubMed] [Europe PMC] [Abstract]

"A basic transthyretin variant (Glu61-->Lys) causes familial amyloidotic polyneuropathy: protein and DNA sequencing and PCR-induced mutation restriction analysis."
Biochem. Biophys. Res. Commun. 194:1090-1096(1993) [PubMed] [Europe PMC] [Abstract]

"Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant."
Br. Heart J. 70:111-115(1993) [PubMed] [Europe PMC] [Abstract]

"Transthyretin Ala-71: a new transthyretin variant in a Spanish family with familial amyloidotic polyneuropathy."
Hum. Mutat. 2:420-421(1993) [PubMed] [Europe PMC] [Abstract]

"A transthyretin variant (alanine 71) associated with familial amyloidotic polyneuropathy in a French family."
J. Med. Genet. 30:120-122(1993) [PubMed] [Europe PMC] [Abstract]

"Gly47Ala: a new transthyretin gene mutation in hereditary amyloidosis TTR-related."
J. Rheumatol. 20:187-187(1993)

"A double-variant transthyretin allele (Ser 6, Ile 33) in the Israeli patient 'SKO' with familial amyloidotic polyneuropathy."
Hum. Mutat. 3:254-260(1994) [PubMed] [Europe PMC] [Abstract]

"Transthyretin VAL107, a new variant associated with familial cardiac and neuropathic amyloidosis."
Hum. Mutat. 3:399-401(1994) [PubMed] [Europe PMC] [Abstract]

"The Ile-84-->Ser amino acid substitution in transthyretin interferes with the interaction with plasma retinol-binding protein."
J. Biol. Chem. 269:23395-23398(1994) [PubMed] [Europe PMC] [Abstract]

"Amyloid polyneuropathy in two German-American families: a new transthyretin variant (Val 107)."
J. Med. Genet. 31:416-417(1994) [PubMed] [Europe PMC] [Abstract]

"Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly)."
J. Neurol. Sci. 121:97-102(1994) [PubMed] [Europe PMC] [Abstract]

"Familial amyloid polyneuropathy in Taiwan: identification of transthyretin variant (Leu55-->Pro)."
Muscle Nerve 17:637-641(1994) [PubMed] [Europe PMC] [Abstract]

"Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant."
Neurology 44:315-318(1994) [PubMed] [Europe PMC] [Abstract]

"Transthyretin gene analysis in European patients with suspected familial amyloid polyneuropathy."
Brain 118:849-856(1995) [PubMed] [Europe PMC] [Abstract]

"A novel variant of transthyretin, 59Thr-->Lys, associated with autosomal dominant cardiac amyloidosis in an Italian family."
Circulation 91:962-967(1995) [PubMed] [Europe PMC] [Abstract]

"Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G)."
Am. J. Pathol. 148:361-366(1996) [PubMed] [Europe PMC] [Abstract]

"Transthyretin amyloidosis: a new mutation associated with dementia."
Ann. Neurol. 41:307-313(1997) [PubMed] [Europe PMC] [Abstract]

"Transthyretin ILE20, a new variant associated with late-onset cardiac amyloidosis."
Hum. Mutat. 9:83-85(1997) [PubMed] [Europe PMC] [Abstract]

"Novel transthyretin missense mutation (Thr34) in an Italian family with hereditary amyloidosis."
Am. J. Med. Genet. 77:135-138(1998) [PubMed] [Europe PMC] [Abstract]

"A novel variant of transthyretin (Glu42Asp) associated with sporadic late-onset cardiac amyloidosis."
Amyloid 5:285-287(1998) [PubMed] [Europe PMC] [Abstract]

"New transthyretin variants Ser 91 and Ser 116 associated with familial amyloidotic polyneuropathy."
Hum. Mutat. 12:71-71(1998) [PubMed] [Europe PMC] [Abstract]

"Transthyretin Ile73Val is associated with familial amyloidotic polyneuropathy in a Bangladeshi family."
Hum. Mutat. 12:135-135(1998) [PubMed] [Europe PMC] [Abstract]

"A new nonamyloid transthyretin variant, G101S, detected by electrospray ionization/mass spectrometry."
Hum. Mutat. 12:363-363(1998) [PubMed] [Europe PMC] [Abstract]

"Transthyretin amyloidosis (serine 44) with headache, hearing loss, and peripheral neuropathy."
Neurology 51:1462-1464(1998) [PubMed] [Europe PMC] [Abstract]

"A new amyloidogenic transthyretin variant (Val122Ala) found in a compound heterozygous patient."
Amyloid 6:54-58(1999) [PubMed] [Europe PMC] [Abstract]

"A new transthyretin variant (Ser23Asn) associated with familial amyloidosis in a Portuguese patient."
Amyloid 6:114-118(1999) [PubMed] [Europe PMC] [Abstract]

"Usefulness of MALDI/TOF mass spectrometry of immunoprecipitated serum variant transthyretin in the diagnosis of familial amyloid polyneuropathy."
Amyloid 6:282-288(1999) [PubMed] [Europe PMC] [Abstract]

"A novel compound heterozygote (FAP ATTR Arg104His/ATTR Val30Met) with high serum transthyretin (TTR) and retinol binding protein (RBP) levels."
Biochem. Biophys. Res. Commun. 264:365-370(1999) [PubMed] [Europe PMC] [Abstract]

"Transthyretin Leu12Pro is associated with systemic, neuropathic and leptomeningeal amyloidosis."
Brain 122:183-190(1999) [PubMed] [Europe PMC] [Abstract]

"Identification of a new transthyretin variant (Ile49) in familial amyloidotic polyneuropathy using electrospray ionization mass spectrometry and nonisotopic RNase cleavage assay."
Hum. Hered. 49:186-189(1999) [PubMed] [Europe PMC] [Abstract]

"A novel variant of transthyretin (Glu89Lys) associated with familial amyloidotic polyneuropathy."
Amyloid 7:46-50(2000) [PubMed] [Europe PMC] [Abstract]

"Heart failure caused by a novel amyloidogenic mutation of the transthyretin gene: ATTR Ala45Ser."
Amyloid 7:137-140(2000) [PubMed] [Europe PMC] [Abstract]

"New transthyretin mutation V28M in a Portuguese kindred with amyloid polyneuropathy."
Muscle Nerve 23:1016-1021(2000) [PubMed] [Europe PMC] [Abstract]

"Recurrent subarachnoid hemorrhage associated with a new transthyretin variant (Gly53Glu)."
Neurology 57:135-137(2001) [PubMed] [Europe PMC] [Abstract]

"A new transthyretin variant Leu55Gln in a patient with systemic amyloidosis."
Amyloid 9:268-271(2002) [PubMed] [