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Protein

Iodotyrosine deiodinase 1

Gene

IYD

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine.1 Publication

Catalytic activityi

L-tyrosine + 2 NADP+ + 2 iodide = 3,5-diiodo-L-tyrosine + 2 NADPH.1 Publication

Cofactori

FMNCurated

Kineticsi

  1. KM=2.67 µM for L-DIT1 Publication
  2. KM=1.35 µM for L-MIT1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei104SubstrateBy similarity1
    Binding sitei161SubstrateBy similarity1
    Binding sitei182SubstrateBy similarity1
    Binding sitei279FMNBy similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi100 – 104FMNBy similarity5
    Nucleotide bindingi127 – 129FMNBy similarity3
    Nucleotide bindingi236 – 239FMNBy similarity4

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Ligandi

    Flavoprotein, FMN, NADP

    Enzyme and pathway databases

    BRENDAi1.22.1.1. 2681.
    ReactomeiR-HSA-209968. Thyroxine biosynthesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Iodotyrosine deiodinase 11 Publication (EC:1.21.1.11 Publication)
    Short name:
    IYD-1
    Alternative name(s):
    Iodotyrosine dehalogenase 1
    Gene namesi
    Name:IYD
    Synonyms:C6orf71, DEHAL1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:21071. IYD.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini24 – 214ExtracellularSequence analysisAdd BLAST191
    Transmembranei215 – 235HelicalSequence analysisAdd BLAST21
    Topological domaini236 – 289CytoplasmicSequence analysisAdd BLAST54

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Thyroid dyshormonogenesis 4 (TDH4)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder due to thyroid dyshormonogenesis, causing severe hypothyroidism, goiter, excessive levels of iodotyrosine in serum and urine, and variable mental deficits derived from unrecognized and untreated hypothyroidism.
    See also OMIM:274800
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_045963101R → W in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration. 1 PublicationCorresponds to variant rs121918138dbSNPEnsembl.1
    Natural variantiVAR_045964105 – 106FI → L in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration. 2
    Natural variantiVAR_045965116I → T in TDH4; strongly reduces activity; marginally respond to the increase of flavin mononucleotide concentration; reduces protein stability. 1 PublicationCorresponds to variant rs121918139dbSNPEnsembl.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi101R → A: Strongly reduces activity. 1 Publication1
    Mutagenesisi101R → H: Reduces activity. 1 Publication1
    Mutagenesisi105F → A: Activity as the wild type. 1 Publication1
    Mutagenesisi105F → Y: Activity as the wild type. 1 Publication1
    Mutagenesisi116I → V: Activity as the wild type. 1 Publication1

    Keywords - Diseasei

    Congenital hypothyroidism, Disease mutation

    Organism-specific databases

    DisGeNETi389434.
    MalaCardsiIYD.
    MIMi274800. phenotype.
    OpenTargetsiENSG00000009765.
    Orphaneti95716. Familial thyroid dyshormonogenesis.
    PharmGKBiPA162392352.

    Polymorphism and mutation databases

    BioMutaiIYD.
    DMDMi91207083.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 23Sequence analysisAdd BLAST23
    ChainiPRO_000023027824 – 289Iodotyrosine deiodinase 1Add BLAST266

    Proteomic databases

    PaxDbiQ6PHW0.
    PeptideAtlasiQ6PHW0.
    PRIDEiQ6PHW0.

    PTM databases

    PhosphoSitePlusiQ6PHW0.

    Expressioni

    Tissue specificityi

    Expressed at a high level in thyroid gland and at lower level in kidney and trachea.1 Publication

    Gene expression databases

    BgeeiENSG00000009765.
    ExpressionAtlasiQ6PHW0. baseline and differential.
    GenevisibleiQ6PHW0. HS.

    Organism-specific databases

    HPAiHPA059627.

    Interactioni

    Subunit structurei

    Homodimer.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TRIM69Q86WT63EBI-10253668,EBI-749955

    Protein-protein interaction databases

    BioGridi133150. 3 interactors.
    IntActiQ6PHW0. 1 interactor.
    STRINGi9606.ENSP00000229447.

    Structurei

    Secondary structure

    1289
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi73 – 75Combined sources3
    Beta strandi77 – 79Combined sources3
    Helixi83 – 98Combined sources16
    Helixi113 – 123Combined sources11
    Helixi129 – 131Combined sources3
    Beta strandi135 – 140Combined sources6
    Helixi143 – 157Combined sources15
    Helixi167 – 172Combined sources6
    Helixi174 – 176Combined sources3
    Helixi184 – 187Combined sources4
    Beta strandi188 – 197Combined sources10
    Beta strandi207 – 209Combined sources3
    Helixi213 – 231Combined sources19
    Helixi244 – 250Combined sources7
    Beta strandi255 – 266Combined sources12
    Beta strandi273 – 275Combined sources3
    Helixi282 – 284Combined sources3
    Beta strandi286 – 289Combined sources4

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4TTBX-ray2.45A/B32-289[»]
    4TTCX-ray2.65A/B/C/D/E/F32-289[»]
    ProteinModelPortaliQ6PHW0.
    SMRiQ6PHW0.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the nitroreductase family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3936. Eukaryota.
    COG0778. LUCA.
    GeneTreeiENSGT00390000004348.
    HOGENOMiHOG000146731.
    HOVERGENiHBG055004.
    InParanoidiQ6PHW0.
    KOiK17231.
    OMAiVHESVGI.
    OrthoDBiEOG091G0CP8.
    PhylomeDBiQ6PHW0.
    TreeFamiTF313415.

    Family and domain databases

    Gene3Di3.40.109.10. 1 hit.
    InterProiIPR029479. Nitroreductase.
    IPR000415. Nitroreductase-like.
    [Graphical view]
    PfamiPF00881. Nitroreductase. 1 hit.
    [Graphical view]
    SUPFAMiSSF55469. SSF55469. 1 hit.

    Sequences (6)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform 1 (identifier: Q6PHW0-1) [UniParc]FASTAAdd to basket

    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

            10         20         30         40         50
    MYFLTPILVA ILCILVVWIF KNADRSMEKK KGEPRTRAEA RPWVDEDLKD
    60 70 80 90 100
    SSDLHQAEED ADEWQESEEN VEHIPFSHNH YPEKEMVKRS QEFYELLNKR
    110 120 130 140 150
    RSVRFISNEQ VPMEVIDNVI RTAGTAPSGA HTEPWTFVVV KDPDVKHKIR
    160 170 180 190 200
    KIIEEEEEIN YMKRMGHRWV TDLKKLRTNW IKEYLDTAPI LILIFKQVHG
    210 220 230 240 250
    FAANGKKKVH YYNEISVSIA CGILLAALQN AGLVTVTTTP LNCGPRLRVL
    260 270 280
    LGRPAHEKLL MLLPVGYPSK EATVPDLKRK PLDQIMVTV
    Length:289
    Mass (Da):33,360
    Last modified:April 4, 2006 - v2
    Checksum:iB73560A682BF6045
    GO
    Isoform 3 (identifier: Q6PHW0-3) [UniParc]FASTAAdd to basket
    Also known as: E

    The sequence of this isoform differs from the canonical sequence as follows:
         230-248: NAGLVTVTTTPLNCGPRLR → VFGKIILKELALISFLNL
         249-289: Missing.

    Show »
    Length:247
    Mass (Da):28,858
    Checksum:i256CCEE175E985A1
    GO
    Isoform 4 (identifier: Q6PHW0-4) [UniParc]FASTAAdd to basket
    Also known as: B

    The sequence of this isoform differs from the canonical sequence as follows:
         230-289: NAGLVTVTTT...KPLDQIMVTV → VNNGITMRHQ...TEGAPGPPRT

    Show »
    Length:293
    Mass (Da):33,781
    Checksum:i2DEF1D502CC9F28E
    GO
    Isoform 5 (identifier: Q6PHW0-5) [UniParc]FASTAAdd to basket
    Also known as: C

    The sequence of this isoform differs from the canonical sequence as follows:
         230-284: NAGLVTVTTT...PDLKRKPLDQ → VNNGITMRHQ...FHFAIEFAAP
         285-289: Missing.

    Show »
    Length:284
    Mass (Da):32,642
    Checksum:i2C8639AEB123CF4F
    GO
    Isoform 6 (identifier: Q6PHW0-6) [UniParc]FASTAAdd to basket
    Also known as: D

    The sequence of this isoform differs from the canonical sequence as follows:
         230-270: NAGLVTVTTT...MLLPVGYPSK → VNNGITMRHQ...SSQGRPGFYC
         271-289: Missing.

    Show »
    Length:270
    Mass (Da):31,367
    Checksum:i501B6AC58642354A
    GO
    Isoform 7 (identifier: Q6PHW0-7) [UniParc]FASTAAdd to basket
    Also known as: F

    The sequence of this isoform differs from the canonical sequence as follows:
         1-55: Missing.
         56-61: QAEEDA → MKEADV
         230-248: NAGLVTVTTTPLNCGPRLR → VFGKIILKELALISFLNL
         249-289: Missing.

    Show »
    Length:192
    Mass (Da):22,460
    Checksum:i5EFAEB7D3AF9FFBC
    GO

    Sequence cautioni

    The sequence AAY41467 differs from that shown. Reason: Erroneous translation.Curated
    The sequence BAC85255 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Isoform 4 (identifier: Q6PHW0-4)
    Sequence conflicti265C → R in AAP22073 (Ref. 1) Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_045963101R → W in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration. 1 PublicationCorresponds to variant rs121918138dbSNPEnsembl.1
    Natural variantiVAR_045964105 – 106FI → L in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration. 2
    Natural variantiVAR_045965116I → T in TDH4; strongly reduces activity; marginally respond to the increase of flavin mononucleotide concentration; reduces protein stability. 1 PublicationCorresponds to variant rs121918139dbSNPEnsembl.1
    Natural variantiVAR_025785260L → P.1 PublicationCorresponds to variant rs17854906dbSNPEnsembl.1
    Natural variantiVAR_045966271E → K.Corresponds to variant rs36063028dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0178021 – 55Missing in isoform 7. 1 PublicationAdd BLAST55
    Alternative sequenceiVSP_01780356 – 61QAEEDA → MKEADV in isoform 7. 1 Publication6
    Alternative sequenceiVSP_017805230 – 289NAGLV…IMVTV → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGCPECR SGDCHYHSSQLWPSTEGAPG PPRT in isoform 4. 1 PublicationAdd BLAST60
    Alternative sequenceiVSP_017806230 – 284NAGLV…KPLDQ → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGRPGAS AAGSLFHFAIEFAAP in isoform 5. 1 PublicationAdd BLAST55
    Alternative sequenceiVSP_017807230 – 270NAGLV…GYPSK → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGRPGFY C in isoform 6. 1 PublicationAdd BLAST41
    Alternative sequenceiVSP_017809230 – 248NAGLV…GPRLR → VFGKIILKELALISFLNL in isoform 3 and isoform 7. 1 PublicationAdd BLAST19
    Alternative sequenceiVSP_017810249 – 289Missing in isoform 3 and isoform 7. 1 PublicationAdd BLAST41
    Alternative sequenceiVSP_017812271 – 289Missing in isoform 6. 1 PublicationAdd BLAST19
    Alternative sequenceiVSP_017813285 – 289Missing in isoform 5. 1 Publication5

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY259176 mRNA. Translation: AAP22072.1.
    AY259177 mRNA. Translation: AAP22073.1.
    AY424901 mRNA. Translation: AAR84259.1.
    AY424902 mRNA. Translation: AAR84260.1.
    AY957659 mRNA. Translation: AAY41465.1.
    AY957660 mRNA. Translation: AAY41466.1.
    AY957661 mRNA. Translation: AAY41467.1. Sequence problems.
    AL031010 Genomic DNA. No translation available.
    BC056253 mRNA. Translation: AAH56253.1.
    AK129950 mRNA. Translation: BAC85255.1. Different initiation.
    CCDSiCCDS5227.1. [Q6PHW0-1]
    CCDS55066.1. [Q6PHW0-3]
    CCDS55067.1. [Q6PHW0-4]
    RefSeqiNP_001158166.1. NM_001164694.1. [Q6PHW0-4]
    NP_001158167.1. NM_001164695.1. [Q6PHW0-3]
    NP_001305424.1. NM_001318495.1.
    NP_981932.1. NM_203395.2. [Q6PHW0-1]
    UniGeneiHs.310225.

    Genome annotation databases

    EnsembliENST00000229447; ENSP00000229447; ENSG00000009765. [Q6PHW0-4]
    ENST00000344419; ENSP00000343763; ENSG00000009765. [Q6PHW0-1]
    ENST00000367335; ENSP00000356304; ENSG00000009765. [Q6PHW0-3]
    ENST00000392256; ENSP00000376085; ENSG00000009765. [Q6PHW0-3]
    GeneIDi389434.
    KEGGihsa:389434.
    UCSCiuc003qnu.3. human. [Q6PHW0-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AY259176 mRNA. Translation: AAP22072.1.
    AY259177 mRNA. Translation: AAP22073.1.
    AY424901 mRNA. Translation: AAR84259.1.
    AY424902 mRNA. Translation: AAR84260.1.
    AY957659 mRNA. Translation: AAY41465.1.
    AY957660 mRNA. Translation: AAY41466.1.
    AY957661 mRNA. Translation: AAY41467.1. Sequence problems.
    AL031010 Genomic DNA. No translation available.
    BC056253 mRNA. Translation: AAH56253.1.
    AK129950 mRNA. Translation: BAC85255.1. Different initiation.
    CCDSiCCDS5227.1. [Q6PHW0-1]
    CCDS55066.1. [Q6PHW0-3]
    CCDS55067.1. [Q6PHW0-4]
    RefSeqiNP_001158166.1. NM_001164694.1. [Q6PHW0-4]
    NP_001158167.1. NM_001164695.1. [Q6PHW0-3]
    NP_001305424.1. NM_001318495.1.
    NP_981932.1. NM_203395.2. [Q6PHW0-1]
    UniGeneiHs.310225.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    4TTBX-ray2.45A/B32-289[»]
    4TTCX-ray2.65A/B/C/D/E/F32-289[»]
    ProteinModelPortaliQ6PHW0.
    SMRiQ6PHW0.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi133150. 3 interactors.
    IntActiQ6PHW0. 1 interactor.
    STRINGi9606.ENSP00000229447.

    PTM databases

    PhosphoSitePlusiQ6PHW0.

    Polymorphism and mutation databases

    BioMutaiIYD.
    DMDMi91207083.

    Proteomic databases

    PaxDbiQ6PHW0.
    PeptideAtlasiQ6PHW0.
    PRIDEiQ6PHW0.

    Protocols and materials databases

    DNASUi389434.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000229447; ENSP00000229447; ENSG00000009765. [Q6PHW0-4]
    ENST00000344419; ENSP00000343763; ENSG00000009765. [Q6PHW0-1]
    ENST00000367335; ENSP00000356304; ENSG00000009765. [Q6PHW0-3]
    ENST00000392256; ENSP00000376085; ENSG00000009765. [Q6PHW0-3]
    GeneIDi389434.
    KEGGihsa:389434.
    UCSCiuc003qnu.3. human. [Q6PHW0-1]

    Organism-specific databases

    CTDi389434.
    DisGeNETi389434.
    GeneCardsiIYD.
    H-InvDBHIX0025059.
    HGNCiHGNC:21071. IYD.
    HPAiHPA059627.
    MalaCardsiIYD.
    MIMi274800. phenotype.
    612025. gene.
    neXtProtiNX_Q6PHW0.
    OpenTargetsiENSG00000009765.
    Orphaneti95716. Familial thyroid dyshormonogenesis.
    PharmGKBiPA162392352.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3936. Eukaryota.
    COG0778. LUCA.
    GeneTreeiENSGT00390000004348.
    HOGENOMiHOG000146731.
    HOVERGENiHBG055004.
    InParanoidiQ6PHW0.
    KOiK17231.
    OMAiVHESVGI.
    OrthoDBiEOG091G0CP8.
    PhylomeDBiQ6PHW0.
    TreeFamiTF313415.

    Enzyme and pathway databases

    BRENDAi1.22.1.1. 2681.
    ReactomeiR-HSA-209968. Thyroxine biosynthesis.

    Miscellaneous databases

    ChiTaRSiIYD. human.
    GeneWikiiIodotyrosine_deiodinase.
    GenomeRNAii389434.
    PROiQ6PHW0.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000009765.
    ExpressionAtlasiQ6PHW0. baseline and differential.
    GenevisibleiQ6PHW0. HS.

    Family and domain databases

    Gene3Di3.40.109.10. 1 hit.
    InterProiIPR029479. Nitroreductase.
    IPR000415. Nitroreductase-like.
    [Graphical view]
    PfamiPF00881. Nitroreductase. 1 hit.
    [Graphical view]
    SUPFAMiSSF55469. SSF55469. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiIYD1_HUMAN
    AccessioniPrimary (citable) accession number: Q6PHW0
    Secondary accession number(s): C9JFW2
    , Q2VPW0, Q2VPW1, Q5F1L5, Q5F1L6, Q5THM4, Q6ZP69, Q7Z7D7, Q7Z7D8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 4, 2006
    Last sequence update: April 4, 2006
    Last modified: November 2, 2016
    This is version 123 of the entry and version 2 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 6
      Human chromosome 6: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.