IOD3_RAT
ID IOD3_RAT Reviewed; 304 AA.
AC P49897;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 3.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Thyroxine 5-deiodinase;
DE EC=1.21.99.3 {ECO:0000269|PubMed:7053997};
DE AltName: Full=5DIII;
DE AltName: Full=DIOIII;
DE AltName: Full=Type 3 DI;
DE AltName: Full=Type III iodothyronine deiodinase;
GN Name=Dio3; Synonyms=Itdi3, Txdi3;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 11-304, FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, TISSUE SPECIFICITY, SELENOCYSTEINE AT SEC-170, AND MUTAGENESIS
RP OF SEC-170.
RC STRAIN=Sprague-Dawley; TISSUE=Skin;
RX PubMed=7622463; DOI=10.1074/jbc.270.28.16569;
RA Croteau W., Whittemore S.L., Schneider M.J., St Germain D.L.;
RT "Cloning and expression of a cDNA for a mammalian type III iodothyronine
RT deiodinase.";
RL J. Biol. Chem. 270:16569-16575(1995).
RN [3]
RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=Sprague-Dawley;
RX PubMed=7053997; DOI=10.1210/endo-110-1-89;
RA Chopra I.J., Chua Teco G.N.;
RT "Characteristics of inner ring (3 or 5) monodeiodination of 3,5-
RT diiodothyronine in rat liver: evidence suggesting marked similarities of
RT inner and outer ring deiodinases for iodothyronines.";
RL Endocrinology 110:89-97(1982).
CC -!- FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'-
CC tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3
CC (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2
CC are inactive metabolites. May play a role in preventing premature
CC exposure of developing fetal tissues to adult levels of thyroid
CC hormones. Can regulate circulating fetal thyroid hormone concentrations
CC throughout gestation. Essential role for regulation of thyroid hormone
CC inactivation during embryological development.
CC {ECO:0000269|PubMed:7622463}.
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:0000269|PubMed:7053997};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.25 uM for 3,5-diiodo-L-thyronine {ECO:0000269|PubMed:7053997};
CC Vmax=25 pmol/min/mg enzyme towards 3-iodo-L-thyronine
CC {ECO:0000269|PubMed:7053997};
CC Note=The kcat/KM ratio for 5 deiodination of T3 is over 1'000-fold
CC that of 5'-deiodination of reverse T3. {ECO:0000269|PubMed:7622463};
CC pH dependence:
CC Optimum pH is 8.3. {ECO:0000269|PubMed:7053997};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:7053997};
CC -!- SUBUNIT: Homodimer. May undergo minor heretodimerization with DIO1 and
CC DIO2. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:7053997};
CC Single-pass type II membrane protein {ECO:0000250}. Endosome membrane
CC {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Neonatal skin, placenta, skeletal muscle and
CC cerebral cortex. {ECO:0000269|PubMed:7622463}.
CC -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-27 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC52241.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AABR06046288; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U24282; AAC52241.2; ALT_INIT; mRNA.
DR PIR; A57240; A57240.
DR RefSeq; NP_058906.3; NM_017210.4.
DR PhosphoSitePlus; P49897; -.
DR Ensembl; ENSRNOT00000078113; ENSRNOP00000093110; ENSRNOG00000052017.
DR GeneID; 29475; -.
DR KEGG; rno:29475; -.
DR CTD; 1735; -.
DR RGD; 68420; Dio3.
DR GeneTree; ENSGT00940000154482; -.
DR InParanoid; P49897; -.
DR OrthoDB; 977776at2759; -.
DR BRENDA; 1.21.99.3; 5301.
DR Reactome; R-RNO-350864; Regulation of thyroid hormone activity.
DR PRO; PR:P49897; -.
DR Proteomes; UP000002494; Chromosome 6.
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; ISO:RGD.
DR GO; GO:0033798; F:thyroxine 5-deiodinase activity; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISO:RGD.
DR GO; GO:0070342; P:brown fat cell proliferation; IEP:RGD.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0097474; P:retinal cone cell apoptotic process; ISO:RGD.
DR GO; GO:0046549; P:retinal cone cell development; ISO:RGD.
DR GO; GO:0042404; P:thyroid hormone catabolic process; ISO:RGD.
DR GO; GO:0042403; P:thyroid hormone metabolic process; ISO:RGD.
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..304
FT /note="Thyroxine 5-deiodinase"
FT /id="PRO_0000154325"
FT TOPO_DOM 1..42
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..62
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 63..304
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 77..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 170
FT NON_STD 170
FT /note="Selenocysteine"
FT MUTAGEN 170
FT /note="U->L: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:7622463"
SQ SEQUENCE 304 AA; 34096 MW; 899DC2E9B4104A15 CRC64;
MPRQAASRLV VGEGEGPPGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP RFLGTAFMLW
LLDFLCIRKH FLRRRHPDHP EPEVELNSEG EEMPPDDPPI CVSDDNRLCT LASLKAVWHG
QKLDFFKQAH EGGPAPNSEV VRPDGFQSQR ILDYAQGTRP LVLNFGSCTU PPFMARMSAF
QRLVTKYQRD VDFLIIYIEE AHPSDGWVTT DSPYVIPQHR SLEDRVSAAR VLQQGAPGCA
LVLDTMANSS SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGTR
PRRL
