IOD2_RAT
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 03-AUG-2022, entry version 140.
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 Ensembl; ENSRNOT00000099607; ENSRNOP00000093973; ENSRNOG00000062383.
DR GeneID; 65162; -.
DR KEGG; rno:65162; -.
DR UCSC; RGD:68418; rat.
DR CTD; 1734; -.
DR RGD; 68418; Dio2.
DR GeneTree; ENSGT00940000154482; -.
DR InParanoid; P70551; -.
DR OrthoDB; 977776at2759; -.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0009409; P:response to cold; IDA:RGD.
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 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 PIRSF; PIRSF001330; IOD; 1.
DR SUPFAM; SSF52833; SSF52833; 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
