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Q92813

- IOD2_HUMAN

UniProt

Q92813 - IOD2_HUMAN

Protein

Type II iodothyronine deiodinase

Gene

DIO2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 135 (01 Oct 2014)
      Sequence version 4 (26 Feb 2008)
      Previous versions | rss
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    Functioni

    Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.

    Catalytic activityi

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei133 – 1331

    GO - Molecular functioni

    1. selenium binding Source: UniProtKB
    2. thyroxine 5'-deiodinase activity Source: UniProtKB
    3. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

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

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Thyroid hormones biosynthesis

    Enzyme and pathway databases

    BioCyciMetaCyc:HS00008-MONOMER.
    BRENDAi1.97.1.10. 2681.
    ReactomeiREACT_15297. Regulation of thyroid hormone activity.
    SABIO-RKQ92813.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Type II iodothyronine deiodinase (EC:1.97.1.10)
    Alternative name(s):
    5DII
    DIOII
    Type 2 DI
    Type-II 5'-deiodinase
    Gene namesi
    Name:DIO2
    Synonyms:ITDI2, TXDI2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:2884. DIO2.

    Subcellular locationi

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27338.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 273273Type II iodothyronine deiodinasePRO_0000154317Add
    BLAST

    Post-translational modificationi

    Ubiquitinated by MARCH6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33.2 Publications

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    PaxDbiQ92813.
    PRIDEiQ92813.

    Expressioni

    Tissue specificityi

    Heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain.

    Gene expression databases

    ArrayExpressiQ92813.
    BgeeiQ92813.
    CleanExiHS_DIO2.
    GenevestigatoriQ92813.

    Organism-specific databases

    HPAiHPA029544.

    Interactioni

    Subunit structurei

    Interacts with USP20 and USP33. Interacts with MARCH6.2 Publications

    Protein-protein interaction databases

    BioGridi108078. 15 interactions.
    STRINGi9606.ENSP00000373490.

    Structurei

    3D structure databases

    ProteinModelPortaliQ92813.
    ModBaseiSearch...
    MobiDBiSearch...

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei10 – 3425HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the iodothyronine deiodinase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG146259.
    HOGENOMiHOG000007088.
    HOVERGENiHBG000099.
    InParanoidiQ92813.
    KOiK17904.
    OrthoDBiEOG7XPZ7H.
    PhylomeDBiQ92813.
    TreeFamiTF329721.

    Family and domain databases

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

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q92813-1) [UniParc]FASTAAdd to Basket

    Also known as: hDII-a

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGILSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVVLL LSRSKSTRGE    50
    WRRMLTSEGL RCVWKSFLLD AYKQVKLGED APNSSVVHVS STEGGDNSGN 100
    GTQEKIAEGA TCHLLDFASP ERPLVVNFGS ATUPPFTSQL PAFRKLVEEF 150
    SSVADFLLVY IDEAHPSDGW AIPGDSSLSF EVKKHQNQED RCAAAQQLLE 200
    RFSLPPQCRV VADRMDNNAN IAYGVAFERV CIVQRQKIAY LGGKGPFSYN 250
    LQEVRHWLEK NFSKRUKKTR LAG 273
    Length:273
    Mass (Da):30,552
    Last modified:February 26, 2008 - v4
    Checksum:i88D68B9AA6CB2A42
    GO
    Isoform 2 (identifier: Q92813-2) [UniParc]FASTAAdd to Basket

    Also known as: hDII-b

    The sequence of this isoform differs from the canonical sequence as follows:
         74-74: Q → QLNCPPSGFSKDGHILCLVYEAYKSRLLVYSHLDLWM

    Note: Has a Sec in positions 169 and 302.

    Show »
    Length:309
    Mass (Da):34,704
    Checksum:i9D9FC1EA33A4E5FB
    GO

    Sequence cautioni

    The sequence AAC95470.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti198 – 1981L → P in BAB16838. (PubMed:11165050)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti81 – 811A → D.
    Corresponds to variant rs2839859 [ dbSNP | Ensembl ].
    VAR_049640
    Natural varianti92 – 921T → A.
    Corresponds to variant rs225014 [ dbSNP | Ensembl ].
    VAR_047549

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei74 – 741Q → QLNCPPSGFSKDGHILCLVY EAYKSRLLVYSHLDLWM in isoform 2. 1 PublicationVSP_026154

    Non-standard residue

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Non-standard residuei133 – 1331Selenocysteine
    Non-standard residuei266 – 2661Selenocysteine

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U53506 mRNA. Translation: AAC50663.1.
    AF093774 mRNA. Translation: AAC95470.1. Different initiation.
    AB041843 mRNA. Translation: BAB16838.1.
    AC007372 Genomic DNA. Translation: AAD45494.1.
    AC010849 Genomic DNA. No translation available.
    AL049837 Genomic DNA. No translation available.
    BC074882 mRNA. Translation: AAH74882.1.
    BC136514 mRNA. Translation: AAI36515.1.
    CCDSiCCDS45146.1. [Q92813-1]
    CCDS55934.1. [Q92813-2]
    RefSeqiNP_000784.2. NM_000793.5. [Q92813-1]
    NP_001007024.1. NM_001007023.3.
    NP_001229431.1. NM_001242502.1.
    NP_001229432.1. NM_001242503.1.
    NP_054644.1. NM_013989.4. [Q92813-1]
    UniGeneiHs.202354.
    Hs.708526.
    Hs.732170.

    Genome annotation databases

    EnsembliENST00000438257; ENSP00000405854; ENSG00000211448. [Q92813-1]
    ENST00000557010; ENSP00000451419; ENSG00000211448. [Q92813-1]
    GeneIDi1734.
    KEGGihsa:1734.
    UCSCiuc010asy.3. human. [Q92813-1]
    uc021rxa.1. human. [Q92813-2]

    Polymorphism databases

    DMDMi172045839.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism, Selenocysteine

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U53506 mRNA. Translation: AAC50663.1 .
    AF093774 mRNA. Translation: AAC95470.1 . Different initiation.
    AB041843 mRNA. Translation: BAB16838.1 .
    AC007372 Genomic DNA. Translation: AAD45494.1 .
    AC010849 Genomic DNA. No translation available.
    AL049837 Genomic DNA. No translation available.
    BC074882 mRNA. Translation: AAH74882.1 .
    BC136514 mRNA. Translation: AAI36515.1 .
    CCDSi CCDS45146.1. [Q92813-1 ]
    CCDS55934.1. [Q92813-2 ]
    RefSeqi NP_000784.2. NM_000793.5. [Q92813-1 ]
    NP_001007024.1. NM_001007023.3.
    NP_001229431.1. NM_001242502.1.
    NP_001229432.1. NM_001242503.1.
    NP_054644.1. NM_013989.4. [Q92813-1 ]
    UniGenei Hs.202354.
    Hs.708526.
    Hs.732170.

    3D structure databases

    ProteinModelPortali Q92813.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108078. 15 interactions.
    STRINGi 9606.ENSP00000373490.

    Polymorphism databases

    DMDMi 172045839.

    Proteomic databases

    PaxDbi Q92813.
    PRIDEi Q92813.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000438257 ; ENSP00000405854 ; ENSG00000211448 . [Q92813-1 ]
    ENST00000557010 ; ENSP00000451419 ; ENSG00000211448 . [Q92813-1 ]
    GeneIDi 1734.
    KEGGi hsa:1734.
    UCSCi uc010asy.3. human. [Q92813-1 ]
    uc021rxa.1. human. [Q92813-2 ]

    Organism-specific databases

    CTDi 1734.
    GeneCardsi GC14M080663.
    HGNCi HGNC:2884. DIO2.
    HPAi HPA029544.
    MIMi 601413. gene.
    neXtProti NX_Q92813.
    PharmGKBi PA27338.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG146259.
    HOGENOMi HOG000007088.
    HOVERGENi HBG000099.
    InParanoidi Q92813.
    KOi K17904.
    OrthoDBi EOG7XPZ7H.
    PhylomeDBi Q92813.
    TreeFami TF329721.

    Enzyme and pathway databases

    BioCyci MetaCyc:HS00008-MONOMER.
    BRENDAi 1.97.1.10. 2681.
    Reactomei REACT_15297. Regulation of thyroid hormone activity.
    SABIO-RK Q92813.

    Miscellaneous databases

    GeneWikii DIO2.
    GenomeRNAii 1734.
    NextBioi 35516965.
    PROi Q92813.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q92813.
    Bgeei Q92813.
    CleanExi HS_DIO2.
    Genevestigatori Q92813.

    Family and domain databases

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

    Publicationsi

    1. "Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues."
      Croteau W., Davey J.C., Galton V.A., St Germain D.L.
      J. Clin. Invest. 98:405-417(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "The 3'-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element."
      Buettner C., Harney J.W., Larsen P.R.
      J. Biol. Chem. 273:33374-33378(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA."
      Ohba K., Yoshioka T., Muraki T.
      Mol. Cell. Endocrinol. 172:169-175(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Umbilical vein.
    4. "Sequencing of human chromosome 14q31 region."
      Dickhoff R., Madan A., Qin S., Abbasi N., Dors M., Rowen L., Harrison G., James R., Loretz C., Lasky S., Madan A., Prescott S., Ratcliffe A., Shaffer T., Hood L.
      Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "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].
    6. "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] (ISOFORM 1).
      Tissue: Lung and Testis.
    7. "Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation."
      Curcio-Morelli C., Zavacki A.M., Christofollete M., Gereben B., de Freitas B.C., Harney J.W., Li Z., Wu G., Bianco A.C.
      J. Clin. Invest. 112:189-196(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP20 AND USP33, INTERACTION WITH USP20 AND USP33.
    8. "The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase."
      Zavacki A.M., Arrojo E Drigo R., Freitas B.C., Chung M., Harney J.W., Egri P., Wittmann G., Fekete C., Gereben B., Bianco A.C.
      Mol. Cell. Biol. 29:5339-5347(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY MARCH6, INTERACTION WITH MARCH6.

    Entry informationi

    Entry nameiIOD2_HUMAN
    AccessioniPrimary (citable) accession number: Q92813
    Secondary accession number(s): B9EGK0
    , G3V315, Q6B0A3, Q9HCP8, Q9P1W4, Q9UDZ1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: February 26, 2008
    Last modified: October 1, 2014
    This is version 135 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

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

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

    External Data

    Dasty 3