ID   TTHY_RAT                Reviewed;         147 AA.
AC   P02767; Q547K9;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 182.
DE   RecName: Full=Transthyretin;
DE   AltName: Full=Prealbumin;
DE   AltName: Full=TBPA;
DE   Flags: Precursor;
GN   Name=Ttr; Synonyms=Tt;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=3922975; DOI=10.1016/s0021-9258(18)88997-9;
RA   Sundelin J., Melhus H., Das S., Eriksson U., Lind P., Traegaardh L.,
RA   Peterson P.A., Rask L.;
RT   "The primary structure of rabbit and rat prealbumin and a comparison with
RT   the tertiary structure of human prealbumin.";
RL   J. Biol. Chem. 260:6481-6487(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3839240; DOI=10.1016/s0021-9258(17)39583-2;
RA   Dickson P.W., Howlett G.J., Schreiber G.;
RT   "Rat transthyretin (prealbumin). Molecular cloning, nucleotide sequence,
RT   and gene expression in liver and brain.";
RL   J. Biol. Chem. 260:8214-8219(1985).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX   PubMed=2734110; DOI=10.1093/nar/17.10.3979;
RA   Duan W., Cole T., Schreiber G.;
RT   "Cloning and nucleotide sequencing of transthyretin (prealbumin) cDNA from
RT   rat choroid plexus and liver.";
RL   Nucleic Acids Res. 17:3979-3979(1989).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley;
RA   Lee Y., Xu C., Zhang Y.;
RT   "Cloning and identification of differential display genes after short
RT   interval successive partial hepatectomy in rat liver regeneration.";
RL   Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Liver;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-23 AND 113-147.
RC   STRAIN=Buffalo; TISSUE=Liver;
RX   PubMed=2891699; DOI=10.1016/s0021-9258(19)57418-x;
RA   Fung W.-P., Thomas T., Dickson P.W., Aldred A.R., Milland J., Dziadek M.,
RA   Power B., Hudson P.J., Schreiber G.;
RT   "Structure and expression of the rat transthyretin (prealbumin) gene.";
RL   J. Biol. Chem. 263:480-488(1988).
RN   [7]
RP   PROTEIN SEQUENCE OF 21-35 AND 38-50, SUBUNIT, INTERACTION WITH RBP4,
RP   SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   TISSUE=Serum;
RX   PubMed=873934; DOI=10.1016/s0021-9258(17)40163-3;
RA   Navab M., Mallia A.K., Kanda Y., Goodman D.S.;
RT   "Rat plasma prealbumin. Isolation and partial characterization.";
RL   J. Biol. Chem. 252:5100-5106(1977).
RN   [8]
RP   PROTEIN SEQUENCE OF 56-90; 101-123 AND 124-147, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA   Lubec G., Afjehi-Sadat L., Lubec S.;
RL   Submitted (SEP-2007) to UniProtKB.
RN   [9]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=2309926; DOI=10.1152/ajpregu.1990.258.2.r338;
RA   Schreiber G., Aldred A.R., Jaworowski A., Nilsson C., Achen M.G.,
RA   Segal M.B.;
RT   "Thyroxine transport from blood to brain via transthyretin synthesis in
RT   choroid plexus.";
RL   Am. J. Physiol. 258:R338-R345(1990).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-72, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), AND SUBUNIT.
RX   PubMed=9511961;
RA   Wojtczak A.;
RT   "Crystal structure of rat transthyretin at 2.5-A resolution: first report
RT   on a unique tetrameric structure.";
RL   Acta Biochim. Pol. 44:505-517(1997).
RN   [12] {ECO:0007744|PDB:1KGI}
RP   X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 21-147 IN COMPLEX WITH
RP   TETRAIODOTHYROACETIC ACID, INTERACTION WITH RETINOL-BINDING PROTEIN, AND
RP   SUBUNIT.
RX   PubMed=11995998;
RA   Muziol T., Cody V., Luft J.R., Pangborn W., Wojtczak A.;
RT   "Complex of rat transthyretin with tetraiodothyroacetic acid refined at 2.1
RT   and 1.8 A resolution.";
RL   Acta Biochim. Pol. 48:877-884(2001).
RN   [13]
RP   STRUCTURE BY NMR OF 125-135 OF FIBRILLAR FORM.
RX   PubMed=14715898; DOI=10.1073/pnas.0304849101;
RA   Jaroniec C.P., MacPhee C.E., Bajaj V.S., McMahon M.T., Dobson C.M.,
RA   Griffin R.G.;
RT   "High-resolution molecular structure of a peptide in an amyloid fibril
RT   determined by magic angle spinning NMR spectroscopy.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:711-716(2004).
CC   -!- FUNCTION: Thyroid hormone-binding protein. Probably transports
CC       thyroxine from the bloodstream to the brain.
CC       {ECO:0000269|PubMed:2309926}.
CC   -!- SUBUNIT: Homotetramer. Dimer of dimers. In the homotetramer, subunits
CC       assemble around a central channel that can accommodate two ligand
CC       molecules. Interacts with RBP4. {ECO:0000269|PubMed:11995998,
CC       ECO:0000269|PubMed:873934, ECO:0000269|PubMed:9511961}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2309926,
CC       ECO:0000269|PubMed:873934}.
CC   -!- TISSUE SPECIFICITY: Detected in serum and cerebrospinal fluid (at
CC       protein level). Highly expressed in the choroid plexus. Detected at
CC       lower levels in the liver. {ECO:0000269|PubMed:2309926,
CC       ECO:0000269|PubMed:2734110, ECO:0000269|PubMed:873934}.
CC   -!- PTM: Sulfonation of the reactive cysteine Cys-30 enhances the stability
CC       of the native conformation of TTR, avoiding misassembly of the protein
CC       leading to amyloid formation. {ECO:0000250|UniProtKB:P02766}.
CC   -!- MISCELLANEOUS: This protein binds retinol-binding protein at levels
CC       similar to, and the thyroid hormones at levels much higher than, the
CC       human protein.
CC   -!- MISCELLANEOUS: Tetramer dissociation and partial unfolding leads to the
CC       formation of aggregates and amyloid fibrils. Small molecules that
CC       occupy at least one of the thyroid hormone binding sites stabilize the
CC       tetramer, and thereby stabilize the native state and protect against
CC       misfolding and the formation of amyloid fibrils (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the transthyretin family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; K03252; AAA41801.1; -; mRNA.
DR   EMBL; K03251; AAA41802.1; -; Genomic_DNA.
DR   EMBL; X14876; CAA33017.1; -; mRNA.
DR   EMBL; AF479660; AAL78377.1; -; mRNA.
DR   EMBL; BC086946; AAH86946.1; -; mRNA.
DR   EMBL; M18685; AAA40708.1; -; Genomic_DNA.
DR   EMBL; M20246; AAA40709.1; -; Genomic_DNA.
DR   PIR; A92542; VBRT.
DR   RefSeq; NP_036813.2; NM_012681.2.
DR   RefSeq; XP_006254519.1; XM_006254457.1.
DR   PDB; 1GKE; X-ray; 2.50 A; A/B/C/D=28-147.
DR   PDB; 1IE4; X-ray; 2.50 A; A/B/C/D=21-147.
DR   PDB; 1KGI; X-ray; 1.80 A; A/B/C/D=21-147.
DR   PDB; 1KGJ; X-ray; 2.30 A; A/B/C/D=21-147.
DR   PDB; 1RVS; NMR; -; A=125-135.
DR   PDB; 2M5K; EM; 12.70 A; A/B/C/D/E/F/G/H=125-135.
DR   PDB; 2M5M; EM; 12.20 A; A/B/C/D/E/F/G/H/I/J/K/L=125-135.
DR   PDB; 3ZPK; NMR; -; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=125-135.
DR   PDBsum; 1GKE; -.
DR   PDBsum; 1IE4; -.
DR   PDBsum; 1KGI; -.
DR   PDBsum; 1KGJ; -.
DR   PDBsum; 1RVS; -.
DR   PDBsum; 2M5K; -.
DR   PDBsum; 2M5M; -.
DR   PDBsum; 3ZPK; -.
DR   AlphaFoldDB; P02767; -.
DR   EMDB; EMD-2323; -.
DR   EMDB; EMD-2324; -.
DR   SMR; P02767; -.
DR   BioGRID; 246973; 1.
DR   IntAct; P02767; 2.
DR   MINT; P02767; -.
DR   STRING; 10116.ENSRNOP00000022113; -.
DR   ChEMBL; CHEMBL2151; -.
DR   TCDB; 9.B.35.1.1; the putative thyronine-transporting transthyretin (transthyretin) family.
DR   GlyCosmos; P02767; 1 site, No reported glycans.
DR   GlyGen; P02767; 1 site.
DR   iPTMnet; P02767; -.
DR   PhosphoSitePlus; P02767; -.
DR   PaxDb; 10116-ENSRNOP00000022113; -.
DR   Ensembl; ENSRNOT00055031120; ENSRNOP00055025087; ENSRNOG00055018337.
DR   Ensembl; ENSRNOT00060021345; ENSRNOP00060016845; ENSRNOG00060012581.
DR   Ensembl; ENSRNOT00065025132; ENSRNOP00065019672; ENSRNOG00065015173.
DR   GeneID; 24856; -.
DR   KEGG; rno:24856; -.
DR   AGR; RGD:3916; -.
DR   CTD; 7276; -.
DR   RGD; 3916; Ttr.
DR   VEuPathDB; HostDB:ENSRNOG00000016275; -.
DR   eggNOG; KOG3006; Eukaryota.
DR   HOGENOM; CLU_115536_2_0_1; -.
DR   InParanoid; P02767; -.
DR   OrthoDB; 5352684at2759; -.
DR   PhylomeDB; P02767; -.
DR   TreeFam; TF300210; -.
DR   Reactome; R-RNO-2453902; The canonical retinoid cycle in rods (twilight vision).
DR   Reactome; R-RNO-6798695; Neutrophil degranulation.
DR   Reactome; R-RNO-975634; Retinoid metabolism and transport.
DR   EvolutionaryTrace; P02767; -.
DR   PRO; PR:P02767; -.
DR   Proteomes; UP000002494; Chromosome 18.
DR   Bgee; ENSRNOG00000016275; Expressed in liver and 19 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IDA:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR   GO; GO:0042562; F:hormone binding; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0070324; F:thyroid hormone binding; IBA:GO_Central.
DR   GO; GO:0006144; P:purine nucleobase metabolic process; IBA:GO_Central.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; TAS:RGD.
DR   CDD; cd05821; TLP_Transthyretin; 1.
DR   Gene3D; 2.60.40.180; Transthyretin/hydroxyisourate hydrolase domain; 1.
DR   InterPro; IPR023418; Thyroxine_BS.
DR   InterPro; IPR000895; Transthyretin/HIU_hydrolase.
DR   InterPro; IPR023416; Transthyretin/HIU_hydrolase_d.
DR   InterPro; IPR036817; Transthyretin/HIU_hydrolase_sf.
DR   InterPro; IPR023419; Transthyretin_CS.
DR   PANTHER; PTHR10395:SF12; TRANSTHYRETIN; 1.
DR   PANTHER; PTHR10395; URICASE AND TRANSTHYRETIN-RELATED; 1.
DR   Pfam; PF00576; Transthyretin; 1.
DR   PRINTS; PR00189; TRNSTHYRETIN.
DR   SMART; SM00095; TR_THY; 1.
DR   SUPFAM; SSF49472; Transthyretin (synonym: prealbumin); 1.
DR   PROSITE; PS00768; TRANSTHYRETIN_1; 1.
DR   PROSITE; PS00769; TRANSTHYRETIN_2; 1.
DR   Genevisible; P02767; RN.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Gamma-carboxyglutamic acid;
KW   Glycoprotein; Hormone; Phosphoprotein; Reference proteome; Secreted;
KW   Signal; Sulfation; Thyroid hormone; Transport.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000269|PubMed:873934"
FT   CHAIN           21..147
FT                   /note="Transthyretin"
FT                   /id="PRO_0000035764"
FT   BINDING         35
FT                   /ligand="L-thyroxine"
FT                   /ligand_id="ChEBI:CHEBI:58448"
FT                   /evidence="ECO:0000305|PubMed:11995998,
FT                   ECO:0007744|PDB:1KGI"
FT   BINDING         74
FT                   /ligand="L-thyroxine"
FT                   /ligand_id="ChEBI:CHEBI:58448"
FT                   /evidence="ECO:0000305|PubMed:11995998"
FT   BINDING         137
FT                   /ligand="L-thyroxine"
FT                   /ligand_id="ChEBI:CHEBI:58448"
FT                   /evidence="ECO:0000305|PubMed:11995998,
FT                   ECO:0007744|PDB:1KGI"
FT   MOD_RES         30
FT                   /note="Sulfocysteine"
FT                   /evidence="ECO:0000250|UniProtKB:P02766"
FT   MOD_RES         62
FT                   /note="4-carboxyglutamate"
FT                   /evidence="ECO:0000250|UniProtKB:P02766"
FT   MOD_RES         72
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   CARBOHYD        118
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        55
FT                   /note="K -> R (in Ref. 1; AAA41801)"
FT                   /evidence="ECO:0000305"
FT   STRAND          31..38
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   TURN            39..42
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          49..55
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          61..68
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   TURN            81..83
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          86..93
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   HELIX           95..101
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          107..118
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          124..132
FT                   /evidence="ECO:0007829|PDB:1KGI"
FT   STRAND          135..143
FT                   /evidence="ECO:0007829|PDB:1KGI"
SQ   SEQUENCE   147 AA;  15720 MW;  67F00D09BCF195BA CRC64;
     MASLRLFLLC LAGLIFASEA GPGGAGESKC PLMVKVLDAV RGSPAVDVAV KVFKKTADGS
     WEPFASGKTA ESGELHGLTT DEKFTEGVYR VELDTKSYWK ALGISPFHEY AEVVFTANDS
     GHRHYTIAAL LSPYSYSTTA VVSNPQN
//