ID   IOD3_XENLA              Reviewed;         271 AA.
AC   P49899;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 2.
DT   03-AUG-2022, entry version 107.
DE   RecName: Full=Thyroxine 5-deiodinase;
DE            EC=1.21.99.3;
DE   AltName: Full=5DIII;
DE   AltName: Full=DIOIII;
DE   AltName: Full=Type 3 DI;
DE   AltName: Full=Type III iodothyronine deiodinase;
DE   AltName: Full=XL-15;
GN   Name=dio3; Synonyms=itdi3, txdi3;
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]
RP   NUCLEOTIDE SEQUENCE [MRNA], SELENOCYSTEINE AT SEC-132, AND MUTAGENESIS OF
RP   SEC-132.
RX   PubMed=8052658; DOI=10.1073/pnas.91.16.7767;
RA   St Germain D.L., Schwartzman R.A., Croteau W., Kanamori A., Wang Z.,
RA   Brown D.D., Galton V.A.;
RT   "A thyroid hormone-regulated gene in Xenopus laevis encodes a type III
RT   iodothyronine 5-deiodinase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:7767-7771(1994).
RN   [2]
RP   ERRATUM OF PUBMED:8052658.
RX   PubMed=7972049; DOI=10.1073/pnas.91.23.11282;
RA   St Germain D.L., Schwartzman R.A., Croteau W., Kanamori A., Wang Z.,
RA   Brown D.D., Galton V.A.;
RL   Proc. Natl. Acad. Sci. U.S.A. 91:11282-11282(1994).
CC   -!- FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'-
CC       tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 into
CC       T2 (3,3'-diiodothyronine). May play a protective role in selected
CC       tissues by preventing their exposure to inappropriately timed or
CC       excessive levels of thyroid hormone. {ECO:0000250|UniProtKB:P49897}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3',5'-triiodo-L-thyronine + A + H(+) + iodide = AH2 + L-
CC         thyroxine; Xref=Rhea:RHEA:18897, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16382, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:57261, ChEBI:CHEBI:58448; EC=1.21.99.3;
CC         Evidence={ECO:0000250|UniProtKB:P49897};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type II
CC       membrane protein {ECO:0000250}. Endosome membrane {ECO:0000250};
CC       Single-pass type II membrane protein {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC       {ECO:0000305}.
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DR   EMBL; L28111; AAA49971.2; -; mRNA.
DR   RefSeq; NP_001081332.1; NM_001087863.1.
DR   DNASU; 397779; -.
DR   GeneID; 397779; -.
DR   KEGG; xla:397779; -.
DR   CTD; 397779; -.
DR   Xenbase; XB-GENE-865707; dio3.L.
DR   OrthoDB; 977776at2759; -.
DR   Proteomes; UP000186698; Chromosome 8L.
DR   Bgee; 397779; Expressed in pancreas and 17 other tissues.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IEA:InterPro.
DR   GO; GO:0033798; F:thyroxine 5-deiodinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   InterPro; IPR000643; Iodothyronine_deiodinase.
DR   InterPro; IPR008261; Iodothyronine_deiodinase_AS.
DR   InterPro; IPR027252; Iodothyronine_deiodinase_I/III.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11781; PTHR11781; 1.
DR   Pfam; PF00837; T4_deiodinase; 1.
DR   PIRSF; PIRSF001330; IOD; 1.
DR   PIRSF; PIRSF500144; IODI_III; 1.
DR   SUPFAM; SSF52833; SSF52833; 1.
DR   PROSITE; PS01205; T4_DEIODINASE; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Endosome; Membrane; Oxidoreductase; Reference proteome;
KW   Selenocysteine; Signal-anchor; Thyroid hormones biosynthesis;
KW   Transmembrane; Transmembrane helix.
FT   CHAIN           1..271
FT                   /note="Thyroxine 5-deiodinase"
FT                   /id="PRO_0000154328"
FT   TOPO_DOM        1..15
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        16..36
FT                   /note="Helical; Signal-anchor for type II membrane protein"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        37..271
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        132
FT   NON_STD         132
FT                   /note="Selenocysteine"
FT   MUTAGEN         132
FT                   /note="U->L: Loss of enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:8052658"
SQ   SEQUENCE   271 AA;  30299 MW;  64D6CE473CA89F1D CRC64;
     MLHCAGPHTG KLVKQVAACC LLLPRFLLTG LMLWLLDFQC IRRRVLLTAR EESTAEHEDP
     PLCVSDSNRM CTVESLRAVW HGQKLDYFKS AHLGCSAPNT EVVMLEGRRL CKILDFSQGK
     RPLVVNFGSC TUPPFMARLQ AYRRLAAQHV GIADFLLVYI EEAHPSDGWL STDASYQIPQ
     HQCLQDRLAA AQLMLQGAPG CRVVVDTMDN SSNAAYGAYF ERLYIVLEGK VVYQGGRGPE
     GYKISELRMW LEQYQQGLMG TKGSGQVVIQ V