ID   IOD2_RAT                Reviewed;         266 AA.
AC   P70551; O70179;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 4.
DT   27-MAR-2024, entry version 147.
DE   RecName: Full=Type II iodothyronine deiodinase;
DE            EC=1.21.99.4;
DE   AltName: Full=5DII;
DE   AltName: Full=DIOII;
DE   AltName: Full=Type 2 DI;
DE   AltName: Full=Type-II 5'-deiodinase;
GN   Name=Dio2; Synonyms=Itdi2, Txdi2;
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], TISSUE SPECIFICITY, AND INDUCTION.
RC   STRAIN=Sprague-Dawley; TISSUE=Brown adipose tissue;
RX   PubMed=8755651; DOI=10.1172/jci118806;
RA   Croteau W., Davey J.C., Galton V.A., St Germain D.L.;
RT   "Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein
RT   differentially expressed and regulated in human and rat brain and other
RT   tissues.";
RL   J. Clin. Invest. 98:405-417(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=9709916; DOI=10.1089/thy.1998.8.615;
RA   Gondou A., Toyoda N., Nishikawa M., Tabata S., Yonemoto T., Ogawa Y.,
RA   Tokoro T., Sakaguchi N., Wang F., Inada M.;
RT   "Induction of type 2 deiodinase activity by cyclic guanosine 3',5'-
RT   monophosphate in cultured rat glial cells.";
RL   Thyroid 8:615-622(1998).
RN   [3]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=9178860; DOI=10.1016/s0304-3940(97)00298-x;
RA   Murakami M., Hosoi Y., Negishi T., Kamiya Y., Ogiwara T., Mizuma H.,
RA   Yamada M., Iriuchijima T., Mori M.;
RT   "Expression and nocturnal increase of type II iodothyronine deiodinase mRNA
RT   in rat pineal gland.";
RL   Neurosci. Lett. 227:65-67(1997).
RN   [4]
RP   TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=19103603; DOI=10.1074/jbc.m808394200;
RA   Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q.,
RA   Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F.,
RA   Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C.;
RT   "Night/day changes in pineal expression of >600 genes: central role of
RT   adrenergic/cAMP signaling.";
RL   J. Biol. Chem. 284:7606-7622(2009).
CC   -!- FUNCTION: Catalyzes the deiodination of T4 (3,5,3',5'-
CC       tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for
CC       providing the brain with appropriate levels of T3 during the critical
CC       period of development.
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   -!- SUBUNIT: Interacts with USP20 and USP33. Interacts with MARCHF6 (By
CC       similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC       protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in cerebral cortex, cerebellum, pituitary
CC       gland, mostly in anterior pituitary gland, and pineal gland, as well as
CC       in brown adipose tissue (BAT). {ECO:0000269|PubMed:19103603,
CC       ECO:0000269|PubMed:8755651, ECO:0000269|PubMed:9178860}.
CC   -!- INDUCTION: In the pineal gland, exhibits night/day variations with a 9-
CC       fold increased expression at night. Up-regulation is due to a large
CC       degree to the release of norepinephrine from nerve terminals in the
CC       pineal gland and cAMP signaling pathway. In BAT, up-regulated in
CC       animals exposed to cold. {ECO:0000269|PubMed:19103603,
CC       ECO:0000269|PubMed:8755651, ECO:0000269|PubMed:9178860}.
CC   -!- PTM: Ubiquitinated by MARCHF6, leading to its degradation by the
CC       proteasome. Deubiquitinated by USP20 and USP33 (By similarity).
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC       {ECO:0000305}.
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DR   EMBL; U53505; AAC52767.1; -; mRNA.
DR   EMBL; AB011068; BAA25186.1; -; mRNA.
DR   PIR; T10816; T10816.
DR   RefSeq; NP_113908.3; NM_031720.4.
DR   STRING; 10116.ENSRNOP00000071065; -.
DR   Ensembl; ENSRNOT00000099607.1; ENSRNOP00000093973.1; ENSRNOG00000062383.1.
DR   Ensembl; ENSRNOT00055045883; ENSRNOP00055037615; ENSRNOG00055026584.
DR   Ensembl; ENSRNOT00060034371; ENSRNOP00060028203; ENSRNOG00060019869.
DR   GeneID; 65162; -.
DR   KEGG; rno:65162; -.
DR   UCSC; RGD:68418; rat.
DR   AGR; RGD:68418; -.
DR   CTD; 1734; -.
DR   RGD; 68418; Dio2.
DR   GeneTree; ENSGT00940000154482; -.
DR   InParanoid; P70551; -.
DR   OMA; KSIWNSF; -.
DR   OrthoDB; 5405869at2759; -.
DR   PhylomeDB; P70551; -.
DR   BRENDA; 1.21.99.4; 5301.
DR   Reactome; R-RNO-350864; Regulation of thyroid hormone activity.
DR   PRO; PR:P70551; -.
DR   Proteomes; UP000002494; Chromosome 6.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IDA:RGD.
DR   GO; GO:0033798; F:thyroxine 5-deiodinase activity; ISO:RGD.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR   GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR   GO; GO:0044255; P:cellular lipid metabolic process; ISO:RGD.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0042404; P:thyroid hormone catabolic process; ISO:RGD.
DR   GO; GO:0006590; P:thyroid hormone generation; IDA:RGD.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; IDA:RGD.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR000643; Iodothyronine_deiodinase.
DR   InterPro; IPR008261; Iodothyronine_deiodinase_AS.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11781; IODOTHYRONINE DEIODINASE; 1.
DR   PANTHER; PTHR11781:SF20; TYPE II IODOTHYRONINE DEIODINASE; 1.
DR   Pfam; PF00837; T4_deiodinase; 1.
DR   PIRSF; PIRSF001330; IOD; 1.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS01205; T4_DEIODINASE; 1.
PE   2: Evidence at transcript level;
KW   Membrane; Oxidoreductase; Reference proteome; Selenocysteine;
KW   Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix;
KW   Ubl conjugation.
FT   CHAIN           1..266
FT                   /note="Type II iodothyronine deiodinase"
FT                   /id="PRO_0000154319"
FT   TRANSMEM        10..34
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        130
FT   NON_STD         130
FT                   /note="Selenocysteine"
FT   NON_STD         263
FT                   /note="Selenocysteine"
FT   CONFLICT        116
FT                   /note="S -> C (in Ref. 2; BAA25186)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   266 AA;  29871 MW;  06DE3292FB467578 CRC64;
     MGLLSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVALL LSRSKSTRGE WRRMLTSEGL
     RCVWNSFLLD AYKQVKLGED APNSSVVHVS NPEAGNNCAS EKTADGAECH LLDFASAERP
     LVVNFGSATU PPFTRQLPAF RQLVEEFSSV ADFLLVYIDE AHPSDGWAVP GDSSMSFEVK
     KHRNQEDRCA AAHQLLERFS LPPQCQVVAD RMDNNANVAY GVAFERVCIV QRRKIAYLGG
     KGPFSYNLQE VRSWLEKNFS KRUILD
//