TTHY_XENLA
ID TTHY_XENLA Reviewed; 153 AA.
AC B7ZS96; Q9W649;
DT 24-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Transthyretin {ECO:0000312|EMBL:AAI70444.1};
DE Short=xTTR {ECO:0000303|PubMed:11080066};
DE AltName: Full=Prealbumin {ECO:0000250|UniProtKB:P02766};
DE Flags: Precursor;
GN Name=ttr;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:BAA77579.1}
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 20-24, FUNCTION, SUBUNIT,
RP INTERACTION WITH RBP4, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MASS SPECTROMETRY.
RC TISSUE=Tadpole liver {ECO:0000269|PubMed:11080066};
RX PubMed=11080066; DOI=10.1152/ajpregu.2000.279.6.r2026;
RA Prapunpoj P., Yamauchi K., Nishiyama N., Richardson S.J., Schreiber G.;
RT "Evolution of structure, ontogeny of gene expression, and function of
RT Xenopus laevis transthyretin.";
RL Am. J. Physiol. 279:R2026-R2041(2000).
RN [2] {ECO:0000312|EMBL:AAI70444.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION, INHIBITION OF TRIIODOTHYRONINE-BINDING, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11017780; DOI=10.1006/gcen.2000.7528;
RA Yamauchi K., Prapunpoj P., Richardson S.J.;
RT "Effect of diethylstilbestrol on thyroid hormone binding to amphibian
RT transthyretins.";
RL Gen. Comp. Endocrinol. 119:329-339(2000).
RN [4] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11335125; DOI=10.1016/s0925-4773(01)00341-0;
RA Zorn A.M., Mason J.;
RT "Gene expression in the embryonic Xenopus liver.";
RL Mech. Dev. 103:153-157(2001).
RN [5] {ECO:0000305}
RP FUNCTION, AND DOMAIN.
RX PubMed=12228058; DOI=10.1152/ajpregu.00042.2002;
RA Prapunpoj P., Richardson S.J., Schreiber G.;
RT "Crocodile transthyretin: structure, function, and evolution.";
RL Am. J. Physiol. 283:R885-R896(2002).
RN [6] {ECO:0000305}
RP FUNCTION, AND INHIBITION OF TRIIODOTHYRONINE-BINDING.
RX PubMed=12553426; DOI=10.1515/cclm.2002.216;
RA Yamauchi K., Eguchi R., Shimada N., Ishihara A.;
RT "The effects of endocrine-disrupting chemicals on thyroid hormone binding
RT to Xenopus laevis transthyretin and thyroid hormone receptor.";
RL Clin. Chem. Lab. Med. 40:1250-1256(2002).
RN [7] {ECO:0000305}
RP FUNCTION, AND INHIBITION OF TRIIODOTHYRONINE-BINDING.
RX PubMed=15590892; DOI=10.1093/toxsci/kfi049;
RA Kudo Y., Yamauchi K.;
RT "In vitro and in vivo analysis of the thyroid disrupting activities of
RT phenolic and phenol compounds in Xenopus laevis.";
RL Toxicol. Sci. 84:29-37(2005).
RN [8] {ECO:0000305}
RP INDUCTION.
RX PubMed=16720020; DOI=10.1016/j.envres.2006.04.001;
RA Lehigh Shirey E.A., Jelaso Langerveld A., Mihalko D., Ide C.F.;
RT "Polychlorinated biphenyl exposure delays metamorphosis and alters thyroid
RT hormone system gene expression in developing Xenopus laevis.";
RL Environ. Res. 102:205-214(2006).
RN [9] {ECO:0000305}
RP FUNCTION, AND INHIBITION OF TRIIODOTHYRONINE-BINDING.
RX PubMed=16627555; DOI=10.1093/toxsci/kfj204;
RA Kudo Y., Yamauchi K., Fukazawa H., Terao Y.;
RT "In vitro and in vivo analysis of the thyroid system-disrupting activities
RT of brominated phenolic and phenol compounds in Xenopus laevis.";
RL Toxicol. Sci. 92:87-95(2006).
RN [10] {ECO:0000305}
RP INDUCTION.
RX PubMed=17157075; DOI=10.1016/j.cbpc.2006.10.008;
RA Urbatzka R., Bottero S., Mandich A., Lutz I., Kloas W.;
RT "Endocrine disrupters with (anti)estrogenic and (anti)androgenic modes of
RT action affecting reproductive biology of Xenopus laevis: I. Effects on sex
RT steroid levels and biomarker expression.";
RL Comp. Biochem. Physiol. 144:310-318(2007).
CC -!- FUNCTION: Thyroid hormone-binding protein, with a much higher binding
CC affinity for triiodothyronine (T3) than for thyroxine (T4). Probably
CC transports triiodothyronine from the bloodstream to the brain.
CC {ECO:0000250|UniProtKB:P02766, ECO:0000269|PubMed:11017780,
CC ECO:0000269|PubMed:11080066, ECO:0000269|PubMed:12228058,
CC ECO:0000269|PubMed:12553426, ECO:0000269|PubMed:15590892,
CC ECO:0000269|PubMed:16627555}.
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:11080066}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11080066}.
CC -!- TISSUE SPECIFICITY: Detected in plasma (at protein level). Expressed
CC during metamorphosis in tadpole liver, but not in tadpole brain nor
CC adult liver. Between 1.5 and 3 days of development, also expressed in
CC the mesoderm of the kidney. {ECO:0000269|PubMed:11017780,
CC ECO:0000269|PubMed:11080066, ECO:0000269|PubMed:11335125}.
CC -!- DEVELOPMENTAL STAGE: Expressed in tadpoles from premetamorphic stage 53
CC until the end of prometamorphic stage 60. Expression levels reach a
CC maximum at prometamorphic stages 58 to 59, then decline gradually
CC during metamorphic climax stages (61-66). Undetectable in adults.
CC {ECO:0000269|PubMed:11017780, ECO:0000269|PubMed:11080066}.
CC -!- INDUCTION: The estrogen ethinylestradiol (EE2) significantly decreases
CC expression in both male and female livers. The environmental
CC contaminants polychlorinated biphenyls (PCBs) result in an increase in
CC gene expression and a delay in metamorphosis.
CC {ECO:0000269|PubMed:16720020, ECO:0000269|PubMed:17157075}.
CC -!- DOMAIN: The N-terminus strongly influences thyroid hormone-binding
CC properties. {ECO:0000269|PubMed:12228058}.
CC -!- MASS SPECTROMETRY: Mass=15013; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:11080066};
CC -!- MISCELLANEOUS: A number of compounds can compete with and disrupt
CC triiodothyronine (T3)-binding. Binds the synthetic estrogen
CC diethylstilbestrol (DES) with the same affinity as T3. Phenolic and
CC phenol compounds can also disrupt T3-binding, with brominated
CC derivatives of bisphenol A (e.g. 3,3'5-tribromobisphenol A) having a
CC higher binding affinity than the chlorinated derivatives (e.g. 3,3'5-
CC trichlorobisphenol A), but with the bromophenols showing lower binding
CC affinity than the chlorophenols. {ECO:0000269|PubMed:11017780,
CC ECO:0000269|PubMed:11080066, ECO:0000269|PubMed:16627555}.
CC -!- SIMILARITY: Belongs to the transthyretin family. {ECO:0000255}.
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DR EMBL; AB026996; BAA77579.1; -; mRNA.
DR EMBL; BC170444; AAI70444.1; -; mRNA.
DR EMBL; BC170446; AAI70446.1; -; mRNA.
DR RefSeq; NP_001081348.1; NM_001087879.1.
DR AlphaFoldDB; B7ZS96; -.
DR SMR; B7ZS96; -.
DR GeneID; 397787; -.
DR KEGG; xla:397787; -.
DR CTD; 397787; -.
DR Xenbase; XB-GENE-865269; ttr.L.
DR OMA; TWEPFAT; -.
DR OrthoDB; 1453185at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 397787; Expressed in liver and 7 other tissues.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0070324; F:thyroid hormone binding; IDA:UniProtKB.
DR GO; GO:0043627; P:response to estrogen; TAS:AgBase.
DR GO; GO:0042572; P:retinol metabolic process; IEA:InterPro.
DR GO; GO:0070327; P:thyroid hormone transport; IC:UniProtKB.
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 Direct protein sequencing; Glycoprotein; Hormone; Reference proteome;
KW Secreted; Signal; Thyroid hormone; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:11080066"
FT CHAIN 20..153
FT /note="Transthyretin"
FT /evidence="ECO:0000269|PubMed:11080066"
FT /id="PRO_0000389429"
FT BINDING 39
FT /ligand="L-thyroxine"
FT /ligand_id="ChEBI:CHEBI:58448"
FT /evidence="ECO:0000250|UniProtKB:P02766"
FT BINDING 78
FT /ligand="L-thyroxine"
FT /ligand_id="ChEBI:CHEBI:58448"
FT /evidence="ECO:0000250|UniProtKB:P02766"
FT BINDING 139..143
FT /ligand="L-thyroxine"
FT /ligand_id="ChEBI:CHEBI:58448"
FT /evidence="ECO:0000250|UniProtKB:P02766"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 128
FT /note="H -> Q (in Ref. 1; BAA77579)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 153 AA; 16692 MW; ED6E32C3DB8E1107 CRC64;
MASFKSFLLL ALLAIVSEAA PPGHASHGEA DSKCPLMVKV LDAVRGIPAA NLLVNVFRQT
ESGKWEQITS GKTTELGEIH NLTTDEQFTE GVYKIEFATK AFWGKLGLSP FHEYVDVVFT
ANDAGHRHYT IAVLLTPYSF SSTAIVSEPH DDL
