IOD3_HUMAN
ID IOD3_HUMAN Reviewed; 304 AA.
AC P55073; G3XAM0; Q8WVN5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 14-MAY-2014, sequence version 4.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Thyroxine 5-deiodinase;
DE EC=1.21.99.3 {ECO:0000269|PubMed:12746313};
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 Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Placenta;
RX PubMed=7593630; DOI=10.1172/jci118299;
RA Salvatore D., Low S.C., Berry M., Maia A.L., Harney J.W., Croteau W.,
RA St Germain D.L., Larsen P.R.;
RT "Type 3 iodothyronine deiodinase: cloning, in vitro expression, and
RT functional analysis of the placental selenoenzyme.";
RL J. Clin. Invest. 96:2421-2430(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-304.
RC TISSUE=Duodenum;
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).
RN [4]
RP MUTAGENESIS OF SEC-170, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=12746313; DOI=10.1210/en.2003-0084;
RA Kuiper G.G., Klootwijk W., Visser T.J.;
RT "Substitution of cysteine for selenocysteine in the catalytic center of
RT type III iodothyronine deiodinase reduces catalytic efficiency and alters
RT substrate preference.";
RL Endocrinology 144:2505-2513(2003).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=12419801; DOI=10.1074/jbc.m210266200;
RA Baqui M., Botero D., Gereben B., Curcio C., Harney J.W., Salvatore D.,
RA Sorimachi K., Larsen P.R., Bianco A.C.;
RT "Human type 3 iodothyronine selenodeiodinase is located in the plasma
RT membrane and undergoes rapid internalization to endosomes.";
RL J. Biol. Chem. 278:1206-1211(2003).
RN [6]
RP SUBUNIT.
RX PubMed=18356288; DOI=10.1210/me.2007-0490;
RA Sagar G.D., Gereben B., Callebaut I., Mornon J.P., Zeold A.,
RA Curcio-Morelli C., Harney J.W., Luongo C., Mulcahey M.A., Larsen P.R.,
RA Huang S.A., Bianco A.C.;
RT "The thyroid hormone-inactivating deiodinase functions as a homodimer.";
RL Mol. Endocrinol. 22:1382-1393(2008).
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:7593630}.
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:12746313};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.3 nM for L-thyroxine {ECO:0000269|PubMed:12746313};
CC Vmax=1.4 pmol/min/mg enzyme {ECO:0000269|PubMed:12746313};
CC -!- SUBUNIT: Homodimer. May undergo minor heretodimerization with DIO1 and
CC DIO2. {ECO:0000269|PubMed:18356288}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12419801};
CC Single-pass type II membrane protein {ECO:0000269|PubMed:12419801}.
CC Endosome membrane {ECO:0000269|PubMed:12419801}; Single-pass type II
CC membrane protein {ECO:0000269|PubMed:12419801}.
CC -!- TISSUE SPECIFICITY: Expressed in placenta and several fetal tissues.
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=AAB35616.2; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=AAH17717.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; S79854; AAB35616.2; ALT_FRAME; mRNA.
DR EMBL; AL049836; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017717; AAH17717.2; ALT_INIT; mRNA.
DR CCDS; CCDS41992.2; -.
DR RefSeq; NP_001353.4; NM_001362.3.
DR BioGRID; 108079; 21.
DR STRING; 9606.ENSP00000427336; -.
DR ChEMBL; CHEMBL3611; -.
DR DrugBank; DB09333; Iopodic acid.
DR DrugBank; DB09100; Thyroid, porcine.
DR iPTMnet; P55073; -.
DR PhosphoSitePlus; P55073; -.
DR BioMuta; DIO3; -.
DR DMDM; 172045679; -.
DR MassIVE; P55073; -.
DR PaxDb; P55073; -.
DR PeptideAtlas; P55073; -.
DR PRIDE; P55073; -.
DR ProteomicsDB; 33783; -.
DR ProteomicsDB; 56777; -.
DR Antibodypedia; 56330; 315 antibodies from 26 providers.
DR DNASU; 1735; -.
DR Ensembl; ENST00000510508.4; ENSP00000427336.3; ENSG00000197406.7.
DR GeneID; 1735; -.
DR KEGG; hsa:1735; -.
DR UCSC; uc021sdx.1; human.
DR CTD; 1735; -.
DR DisGeNET; 1735; -.
DR GeneCards; DIO3; -.
DR HGNC; HGNC:2885; DIO3.
DR HPA; ENSG00000197406; Tissue enhanced (cervix, placenta).
DR MIM; 601038; gene.
DR neXtProt; NX_P55073; -.
DR OpenTargets; ENSG00000197406; -.
DR PharmGKB; PA27339; -.
DR VEuPathDB; HostDB:ENSG00000197406; -.
DR eggNOG; ENOG502S5FA; Eukaryota.
DR GeneTree; ENSGT00940000154482; -.
DR HOGENOM; CLU_089345_0_0_1; -.
DR InParanoid; P55073; -.
DR OMA; FGSCSXP; -.
DR OrthoDB; 977776at2759; -.
DR PhylomeDB; P55073; -.
DR TreeFam; TF329721; -.
DR BioCyc; MetaCyc:HS11928-MON; -.
DR BRENDA; 1.21.99.3; 2681.
DR PathwayCommons; P55073; -.
DR Reactome; R-HSA-350864; Regulation of thyroid hormone activity.
DR SABIO-RK; P55073; -.
DR SIGNOR; P55073; -.
DR BioGRID-ORCS; 1735; 7 hits in 1065 CRISPR screens.
DR GenomeRNAi; 1735; -.
DR Pharos; P55073; Tbio.
DR PRO; PR:P55073; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P55073; protein.
DR Bgee; ENSG00000197406; Expressed in endocervix and 102 other tissues.
DR Genevisible; P55073; HS.
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:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IBA:GO_Central.
DR GO; GO:0033798; F:thyroxine 5-deiodinase activity; IDA:ARUK-UCL.
DR GO; GO:0070342; P:brown fat cell proliferation; IEA:Ensembl.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0097474; P:retinal cone cell apoptotic process; IEA:Ensembl.
DR GO; GO:0046549; P:retinal cone cell development; IEA:Ensembl.
DR GO; GO:0042404; P:thyroid hormone catabolic process; IEA:Ensembl.
DR GO; GO:0042403; P:thyroid hormone metabolic process; IGI:ARUK-UCL.
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_0000154323"
FT TOPO_DOM 1..44
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 45..67
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 68..304
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT ACT_SITE 170
FT NON_STD 170
FT /note="Selenocysteine"
FT MUTAGEN 170
FT /note="U->A: Complete loss of activity."
FT /evidence="ECO:0000269|PubMed:12746313"
FT CONFLICT 29
FT /note="R -> H (in Ref. 1; AAB35616)"
FT /evidence="ECO:0000305"
FT CONFLICT 79
FT /note="Q -> K (in Ref. 1; AAB35616)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 33947 MW; 08B61835B353D3C7 CRC64;
MPRQATSRLV VGEGEGSQGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP RFLGTAFMLW
LLDFLCIRKH FLGRRRRGQP EPEVELNSEG EEVPPDDPPI CVSDDNRLCT LASLKAVWHG
QKLDFFKQAH EGGPAPNSEV VLPDGFQSQH ILDYAQGNRP LVLNFGSCTU PPFMARMSAF
QRLVTKYQRD VDFLIIYIEE AHPSDGWVTT DSPYIIPQHR SLEDRVSAAR VLQQGAPGCA
LVLDTMANSS SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGAR
PRRV
