ID   IOD2_MOUSE              Reviewed;         266 AA.
AC   Q9Z1Y9; Q05A70; Q9JHH1;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 4.
DT   27-MAR-2024, entry version 168.
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;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Brain;
RX   PubMed=9927339; DOI=10.1210/endo.140.2.6678;
RA   Davey J.C., Schneider M.J., Becker K.B., Galton V.A.;
RT   "Cloning of a 5.8 kb cDNA for a mouse type 2 deiodinase.";
RL   Endocrinology 140:1022-1025(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP   SPECIFICITY.
RC   STRAIN=C3H/HeN; TISSUE=Brain;
RX   PubMed=10715551; DOI=10.1016/s0303-7207(99)00249-x;
RA   Song S., Sorimachi K., Adachi K., Oka T.;
RT   "Biochemical and molecular biological evidence for the presence of type II
RT   iodothyronine deiodinase in mouse mammary gland.";
RL   Mol. Cell. Endocrinol. 160:173-181(2000).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Cochlea;
RX   PubMed=10655523; DOI=10.1073/pnas.97.3.1287;
RA   Campos-Barros A., Amma L.L., Faris J.S., Shailam R., Kelley M.W.,
RA   Forrest D.;
RT   "Type 2 iodothyronine deiodinase expression in the cochlea before the onset
RT   of hearing.";
RL   Proc. Natl. Acad. Sci. U.S.A. 97:1287-1292(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
CC   -!- FUNCTION: Responsible for 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. {ECO:0000250}.
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   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=4.4 nM for T4 {ECO:0000269|PubMed:10715551};
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 mammary gland and in brain.
CC       {ECO:0000269|PubMed:10715551}.
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; AF096875; AAD11422.1; -; mRNA.
DR   EMBL; AF177196; AAD53113.1; -; mRNA.
DR   EMBL; AF093137; AAF00069.2; -; mRNA.
DR   EMBL; BC125383; AAI25384.1; -; mRNA.
DR   EMBL; BC125385; AAI25386.1; -; mRNA.
DR   RefSeq; NP_034180.1; NM_010050.3.
DR   STRING; 10090.ENSMUSP00000081013; -.
DR   PaxDb; 10090-ENSMUSP00000081013; -.
DR   ProteomicsDB; 269074; -.
DR   Antibodypedia; 47379; 233 antibodies from 32 providers.
DR   DNASU; 13371; -.
DR   GeneID; 13371; -.
DR   KEGG; mmu:13371; -.
DR   UCSC; uc007okf.1; mouse.
DR   AGR; MGI:1338833; -.
DR   CTD; 1734; -.
DR   MGI; MGI:1338833; Dio2.
DR   VEuPathDB; HostDB:ENSMUSG00000007682; -.
DR   eggNOG; ENOG502QS2F; Eukaryota.
DR   HOGENOM; CLU_089345_1_0_1; -.
DR   InParanoid; Q9Z1Y9; -.
DR   OMA; KSIWNSF; -.
DR   OrthoDB; 5405869at2759; -.
DR   PhylomeDB; Q9Z1Y9; -.
DR   TreeFam; TF329721; -.
DR   BRENDA; 1.21.99.4; 3474.
DR   Reactome; R-MMU-350864; Regulation of thyroid hormone activity.
DR   SABIO-RK; Q9Z1Y9; -.
DR   BioGRID-ORCS; 13371; 0 hits in 80 CRISPR screens.
DR   ChiTaRS; Dio2; mouse.
DR   PRO; PR:Q9Z1Y9; -.
DR   Proteomes; UP000000589; Chromosome 12.
DR   RNAct; Q9Z1Y9; Protein.
DR   Bgee; ENSMUSG00000007682; Expressed in median eminence of neurohypophysis and 152 other cell types or tissues.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IDA:UniProtKB.
DR   GO; GO:0033798; F:thyroxine 5-deiodinase activity; ISO:MGI.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR   GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR   GO; GO:0044255; P:cellular lipid metabolic process; IMP:MGI.
DR   GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR   GO; GO:0042404; P:thyroid hormone catabolic process; IMP:MGI.
DR   GO; GO:0006590; P:thyroid hormone generation; ISO:MGI.
DR   GO; GO:0042403; P:thyroid hormone metabolic process; ISO:MGI.
DR   GO; GO:0070460; P:thyroid-stimulating hormone secretion; TAS:UniProtKB.
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.
DR   Genevisible; Q9Z1Y9; MM.
PE   1: Evidence at protein 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_0000154318"
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"
SQ   SEQUENCE   266 AA;  29929 MW;  B2FD28E171DC5486 CRC64;
     MGLLSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVALL LSRSKSTRGE WRRMLTSEGL
     RCVWNSFLLD AYKQVKLGED APNSSVVHVS NPESGNNYAS EKTADGAECH LLDFASAERP
     LVVNFGSATU PPFTRQLPAF RQLVEEFSSV ADFLLVYIDE AHPSDGWAVP GDSSLSFEVK
     KHRNQEDRCA AAHQLLERFS LPPQCQVVAD RMDNNANVAY GVAFERVCIV QRRKIAYLGG
     KGPFSYNLQE VRSWLEKNFS KRUILD
//