TTHY_RAT
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 03-AUG-2022, entry version 175.
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 -!- 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}.
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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 SMR; P02767; -.
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 GlyGen; P02767; 1 site.
DR iPTMnet; P02767; -.
DR PhosphoSitePlus; P02767; -.
DR PaxDb; P02767; -.
DR PRIDE; P02767; -.
DR GeneID; 24856; -.
DR KEGG; rno:24856; -.
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 OMA; TWEPFAT; -.
DR OrthoDB; 1453185at2759; -.
DR PhylomeDB; P02767; -.
DR TreeFam; TF300210; -.
DR Reactome; R-RNO-2453902; The canonical retinoid cycle in rods (twilight vision).
DR Reactome; R-RNO-3000171; Non-integrin membrane-ECM interactions.
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 tissues.
DR Genevisible; P02767; RN.
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:0042572; P:retinol metabolic process; IEA:InterPro.
DR GO; GO:0042403; P:thyroid hormone metabolic process; TAS:RGD.
DR GO; GO:0070327; P:thyroid hormone transport; IEA:InterPro.
DR Gene3D; 2.60.40.180; -; 1.
DR InterPro; IPR023418; Thyroxine_BS.
DR InterPro; IPR030178; Transthyretin.
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; PTHR10395; 1.
DR PANTHER; PTHR10395:SF12; PTHR10395:SF12; 1.
DR Pfam; PF00576; Transthyretin; 1.
DR PRINTS; PR00189; TRNSTHYRETIN.
DR SMART; SM00095; TR_THY; 1.
DR SUPFAM; SSF49472; SSF49472; 1.
DR PROSITE; PS00768; TRANSTHYRETIN_1; 1.
DR PROSITE; PS00769; TRANSTHYRETIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Gamma-carboxyglutamic acid;
KW Glycoprotein; Hormone; Phosphoprotein; Reference proteome; Secreted;
KW Signal; 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 135..139
FT /ligand="L-thyroxine"
FT /ligand_id="ChEBI:CHEBI:58448"
FT /evidence="ECO:0000305|PubMed:11995998,
FT ECO:0007744|PDB:1KGI"
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
