ID   IOD_HALRO               Reviewed;         259 AA.
AC   Q6U6H1;
DT   07-JUN-2017, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 2.
DT   29-SEP-2021, entry version 55.
DE   RecName: Full=Thyroxine 5'-deiodinase {ECO:0000305};
DE            EC=1.21.99.4 {ECO:0000255|PROSITE-ProRule:PRU10107, ECO:0000269|PubMed:14657009};
DE   AltName: Full=Iodothyronine deiodinase {ECO:0000255|RuleBase:RU000676, ECO:0000303|PubMed:14657009};
OS   Halocynthia roretzi (Sea squirt) (Cynthia roretzi).
OC   Eukaryota; Metazoa; Chordata; Tunicata; Ascidiacea; Stolidobranchia;
OC   Pyuridae; Halocynthia.
OX   NCBI_TaxID=7729 {ECO:0000312|EMBL:AAR25890.1};
RN   [1] {ECO:0000312|EMBL:AAR25890.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND
RP   MUTAGENESIS OF SEC-133.
RX   PubMed=14657009; DOI=10.1210/en.2003-1248;
RA   Shepherdley C.A., Klootwijk W., Makabe K.W., Visser T.J., Kuiper G.G.;
RT   "An ascidian homolog of vertebrate iodothyronine deiodinases.";
RL   Endocrinology 145:1255-1268(2004).
CC   -!- FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'-
CC       tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Can also produce
CC       3,3'-diiodothyronine from reverse T3 (rT3, 3,3',5'-triiodothyronine).
CC       Does not have significant inner-ring deiodination activity for T4, T3
CC       or rT3. {ECO:0000269|PubMed:14657009}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3,3',5-triiodo-L-thyronine + A + H(+) + iodide = AH2 + L-
CC         thyroxine; Xref=Rhea:RHEA:19745, ChEBI:CHEBI:13193,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:16382, ChEBI:CHEBI:17499,
CC         ChEBI:CHEBI:58448, ChEBI:CHEBI:533015; EC=1.21.99.4;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU10107,
CC         ECO:0000269|PubMed:14657009};
CC   -!- ACTIVITY REGULATION: Inhibited by gold thioglucose (GTG) and
CC       iodoacetate (IAc). {ECO:0000269|PubMed:14657009}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=4 uM for T4 {ECO:0000269|PubMed:14657009};
CC         KM=2.5 uM for rT3 {ECO:0000269|PubMed:14657009};
CC         Vmax=30 pmol/min/mg enzyme towards T4 {ECO:0000269|PubMed:14657009};
CC         Vmax=33 pmol/min/mg enzyme towards rT3 {ECO:0000269|PubMed:14657009};
CC       pH dependence:
CC         Optimum pH is 7. {ECO:0000269|PubMed:14657009};
CC       Temperature dependence:
CC         Optimum temperature is 20-30 degrees Celsius.
CC         {ECO:0000269|PubMed:14657009};
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:14657009};
CC       Peripheral membrane protein {ECO:0000305}. Nucleus
CC       {ECO:0000269|PubMed:14657009}.
CC   -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC       {ECO:0000255|RuleBase:RU000676, ECO:0000305}.
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DR   EMBL; AY377937; AAR25890.1; -; mRNA.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IDA:UniProtKB.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   InterPro; IPR000643; Iodothyronine_deiodinase.
DR   InterPro; IPR008261; Iodothyronine_deiodinase_AS.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11781; PTHR11781; 1.
DR   Pfam; PF00837; T4_deiodinase; 1.
DR   SUPFAM; SSF52833; SSF52833; 1.
DR   PROSITE; PS01205; T4_DEIODINASE; 1.
PE   1: Evidence at protein level;
KW   Membrane; Nucleus; Oxidoreductase; Selenocysteine;
KW   Thyroid hormones biosynthesis.
FT   CHAIN           1..259
FT                   /note="Thyroxine 5'-deiodinase"
FT                   /id="PRO_0000440577"
FT   ACT_SITE        133
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10107,
FT                   ECO:0000305|PubMed:14657009"
FT   NON_STD         133
FT                   /note="Selenocysteine"
FT                   /evidence="ECO:0000305|PubMed:14657009"
FT   MUTAGEN         133
FT                   /note="U->C,A: Abolishes catalytic activity."
FT                   /evidence="ECO:0000269|PubMed:14657009"
SQ   SEQUENCE   259 AA;  29676 MW;  9210CA9795ECB772 CRC64;
     MHNLLEIKII RFLRNVFYFL HVLFNECLDT LKAYYKRWRG MKSEKPLDPS SRRARIIQAT
     GVDLSRDPAM QSLRGVYHMA KSILYADVLR TAVRGGNAPN SSLVNYRTKE KCNILDFMKP
     GRPLVVNFGS CSUPPFMASF EIFSRIIDSY HERADFLTVY IEEAHSSDLW ALKNNKYSIP
     SHITFEDRME AAAIFKKSVS FECAFAVDTM KDETNLSYGA LPERTAIILD GKVQYIGGIG
     PFNYDLVELE KELIAVLKK