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P55073

- IOD3_HUMAN

UniProt

P55073 - IOD3_HUMAN

Protein

Type III iodothyronine deiodinase

Gene

DIO3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 139 (01 Oct 2014)
      Sequence version 4 (14 May 2014)
      Previous versions | rss
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    Functioni

    Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.1 Publication

    Catalytic activityi

    3,3',5'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2.

    Kineticsi

    1. KM=4.3 nM for Thyroxine1 Publication

    Vmax=1.4 pmol/min/mg enzyme1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei170 – 1701

    GO - Molecular functioni

    1. thyroxine 5'-deiodinase activity Source: UniProtKB
    2. thyroxine 5-deiodinase activity Source: UniProtKB-EC

    GO - Biological processi

    1. cellular nitrogen compound metabolic process Source: Reactome
    2. hormone biosynthetic process Source: UniProtKB-KW
    3. small molecule metabolic process Source: Reactome
    4. thyroid hormone generation Source: Reactome

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Thyroid hormones biosynthesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS11928-MONOMER.
    ReactomeiREACT_15297. Regulation of thyroid hormone activity.
    SABIO-RKP55073.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Type III iodothyronine deiodinase (EC:1.97.1.11)
    Alternative name(s):
    5DIII
    DIOIII
    Type 3 DI
    Type-III 5'-deiodinase
    Gene namesi
    Name:DIO3
    Synonyms:ITDI3, TXDI3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:2885. DIO3.

    Subcellular locationi

    Cell membrane 1 Publication; Single-pass type II membrane protein 1 Publication. Endosome membrane 1 Publication; Single-pass type II membrane protein 1 Publication

    GO - Cellular componenti

    1. endosome membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Endosome, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi170 – 1701U → A: Complete loss of activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA27339.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 304304Type III iodothyronine deiodinasePRO_0000154323Add
    BLAST

    Proteomic databases

    PaxDbiP55073.
    PRIDEiP55073.

    Expressioni

    Tissue specificityi

    Expressed in placenta and several fetal tissues.

    Gene expression databases

    CleanExiHS_DIO3.
    GenevestigatoriP55073.

    Interactioni

    Subunit structurei

    Homodimer. May undergo minor heretodimerization with DIO1 and DIO2.1 Publication

    Protein-protein interaction databases

    BioGridi108079. 3 interactions.
    STRINGi9606.ENSP00000352273.

    Structurei

    3D structure databases

    ProteinModelPortaliP55073.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4444CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini68 – 304237ExtracellularSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei45 – 6723Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the iodothyronine deiodinase family.Curated

    Keywords - Domaini

    Signal-anchor, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG297144.
    HOGENOMiHOG000007088.
    HOVERGENiHBG000099.
    InParanoidiP55073.
    KOiK07754.
    OrthoDBiEOG79PJQC.
    PhylomeDBiP55073.
    TreeFamiTF329721.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR000643. Iodothyronine_deiodinase.
    IPR008261. Iodothyronine_deiodinase_AS.
    IPR027252. Iodothyronine_deiodinase_I/III.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view]
    PANTHERiPTHR11781. PTHR11781. 1 hit.
    PfamiPF00837. T4_deiodinase. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001330. IOD. 1 hit.
    PIRSF500144. IODI_III. 1 hit.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    PROSITEiPS01205. T4_DEIODINASE. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P55073-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPRQATSRLV VGEGEGSQGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP    50
    RFLGTAFMLW LLDFLCIRKH FLGRRRRGQP EPEVELNSEG EEVPPDDPPI 100
    CVSDDNRLCT LASLKAVWHG QKLDFFKQAH EGGPAPNSEV VLPDGFQSQH 150
    ILDYAQGNRP LVLNFGSCTU PPFMARMSAF QRLVTKYQRD VDFLIIYIEE 200
    AHPSDGWVTT DSPYIIPQHR SLEDRVSAAR VLQQGAPGCA LVLDTMANSS 250
    SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGAR 300
    PRRV 304
    Length:304
    Mass (Da):33,947
    Last modified:May 14, 2014 - v4
    Checksum:i08B61835B353D3C7
    GO

    Sequence cautioni

    The sequence AAB35616.2 differs from that shown. Reason: Frameshift at position 21.
    The sequence AAH17717.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti29 – 291R → H in AAB35616. (PubMed:7593630)Curated
    Sequence conflicti79 – 791Q → K in AAB35616. (PubMed:7593630)Curated

    Non-standard residue

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-standard residuei170 – 1701Selenocysteine

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S79854 mRNA. Translation: AAB35616.2. Frameshift.
    AL049836 Genomic DNA. No translation available.
    BC017717 mRNA. Translation: AAH17717.2. Different initiation.
    CCDSiCCDS41992.2.
    RefSeqiNP_001353.4. NM_001362.3.
    UniGeneiHs.49322.

    Genome annotation databases

    EnsembliENST00000510508; ENSP00000427336; ENSG00000197406.
    GeneIDi1735.
    KEGGihsa:1735.

    Polymorphism databases

    DMDMi172045679.

    Keywords - Coding sequence diversityi

    Selenocysteine

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    S79854 mRNA. Translation: AAB35616.2 . Frameshift.
    AL049836 Genomic DNA. No translation available.
    BC017717 mRNA. Translation: AAH17717.2 . Different initiation.
    CCDSi CCDS41992.2.
    RefSeqi NP_001353.4. NM_001362.3.
    UniGenei Hs.49322.

    3D structure databases

    ProteinModelPortali P55073.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108079. 3 interactions.
    STRINGi 9606.ENSP00000352273.

    Chemistry

    ChEMBLi CHEMBL3611.

    Polymorphism databases

    DMDMi 172045679.

    Proteomic databases

    PaxDbi P55073.
    PRIDEi P55073.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000510508 ; ENSP00000427336 ; ENSG00000197406 .
    GeneIDi 1735.
    KEGGi hsa:1735.

    Organism-specific databases

    CTDi 1735.
    GeneCardsi GC14P102027.
    HGNCi HGNC:2885. DIO3.
    MIMi 601038. gene.
    neXtProti NX_P55073.
    PharmGKBi PA27339.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG297144.
    HOGENOMi HOG000007088.
    HOVERGENi HBG000099.
    InParanoidi P55073.
    KOi K07754.
    OrthoDBi EOG79PJQC.
    PhylomeDBi P55073.
    TreeFami TF329721.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS11928-MONOMER.
    Reactomei REACT_15297. Regulation of thyroid hormone activity.
    SABIO-RK P55073.

    Miscellaneous databases

    GenomeRNAii 1735.
    NextBioi 35517882.
    PROi P55073.
    SOURCEi Search...

    Gene expression databases

    CleanExi HS_DIO3.
    Genevestigatori P55073.

    Family and domain databases

    Gene3Di 3.40.30.10. 1 hit.
    InterProi IPR000643. Iodothyronine_deiodinase.
    IPR008261. Iodothyronine_deiodinase_AS.
    IPR027252. Iodothyronine_deiodinase_I/III.
    IPR012336. Thioredoxin-like_fold.
    [Graphical view ]
    PANTHERi PTHR11781. PTHR11781. 1 hit.
    Pfami PF00837. T4_deiodinase. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001330. IOD. 1 hit.
    PIRSF500144. IODI_III. 1 hit.
    SUPFAMi SSF52833. SSF52833. 1 hit.
    PROSITEi PS01205. T4_DEIODINASE. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme."
      Salvatore D., Low S.C., Berry M., Maia A.L., Harney J.W., Croteau W., St Germain D.L., Larsen P.R.
      J. Clin. Invest. 96:2421-2430(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
      Tissue: Placenta.
    2. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-304.
      Tissue: Duodenum.
    4. "Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference."
      Kuiper G.G., Klootwijk W., Visser T.J.
      Endocrinology 144:2505-2513(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF SEC-170, BIOPHYSICOCHEMICAL PROPERTIES.
    5. "Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes."
      Baqui M., Botero D., Gereben B., Curcio C., Harney J.W., Salvatore D., Sorimachi K., Larsen P.R., Bianco A.C.
      J. Biol. Chem. 278:1206-1211(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    6. Cited for: SUBUNIT.

    Entry informationi

    Entry nameiIOD3_HUMAN
    AccessioniPrimary (citable) accession number: P55073
    Secondary accession number(s): G3XAM0, Q8WVN5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: May 14, 2014
    Last modified: October 1, 2014
    This is version 139 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Caution

    It is uncertain whether Met-1 or Met-27 is the initiator.Curated

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3