The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the conversion of prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer ring 5'-deiodination. This gene is widely expressed, including in thyroid and brain. It is thought to be responsible for the 'local' product... See more...

Aliases for DIO2 Gene

Aliases for DIO2 Gene

  • Iodothyronine Deiodinase 2 2 3 5
  • Deiodinase, Iodothyronine Type II 2 3
  • Type II Iodothyronine Deiodinase 3 4
  • Thyroxine Deiodinase, Type II 2 3
  • Type-II 5'-Deiodinase 3 4
  • Deiodinase-2 2 3
  • Deiodonase-2 2 3
  • Type 2 DI 3 4
  • DIOII 3 4
  • TXDI2 3 4
  • 5DII 3 4
  • Type 2 Iodothyronine Deiodinase 3
  • Type-II 5'Deiodinase 3
  • EC 1.97.1.10 52
  • EC 1.21.99.4 4
  • EC 1.97.1 52
  • ITDI2 4
  • SelY 3
  • D2 3

External Ids for DIO2 Gene

Previous GeneCards Identifiers for DIO2 Gene

  • GC14M078169
  • GC14M074480
  • GC14M078653
  • GC14M079733
  • GC14M080663
  • GC14M060829

Summaries for DIO2 Gene

Entrez Gene Summary for DIO2 Gene

  • The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the conversion of prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer ring 5'-deiodination. This gene is widely expressed, including in thyroid and brain. It is thought to be responsible for the 'local' production of T3, and thus important in influencing thyroid hormone action in these tissues. It has also been reported to be highly expressed in thyroids of patients with Graves disease, and in follicular adenomas. The intrathyroidal T4 to T3 conversion by this enzyme may contribute significantly to the relative increase in thyroidal T3 production in these patients. This protein is a selenoprotein containing the non-standard amino acid, selenocysteine (Sec), which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Unlike the other two members (DIO1 and DIO3) of this enzyme family, the mRNA for this gene contains an additional in-frame UGA codon that has been reported (in human) to function either as a Sec or a stop codon, which can result in two isoforms with one or two Sec residues; however, only the upstream Sec (conserved with the single Sec residue found at the active site in DIO1 and DIO3) was shown to be essential for enzyme activity (PMID:10403186). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2018]

GeneCards Summary for DIO2 Gene

DIO2 (Iodothyronine Deiodinase 2) is a Protein Coding gene. Diseases associated with DIO2 include Graves' Disease and Euthyroid Sick Syndrome. Among its related pathways are Metabolism and Amine-derived hormones. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and antioxidant activity. An important paralog of this gene is DIO3.

UniProtKB/Swiss-Prot Summary for DIO2 Gene

  • 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.

Gene Wiki entry for DIO2 Gene

Additional gene information for DIO2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for DIO2 Gene

Genomics for DIO2 Gene

GeneHancer (GH) Regulatory Elements for DIO2 Gene

Promoters and enhancers for DIO2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14J080211 Promoter/Enhancer 1.4 EPDnew Ensembl ENCODE 504.3 +175.9 175853 1.8 HNRNPK TCF12 EP300 BCL11A DEK ZNF384 BRCA1 CEBPB CHD2 JUN DIO2 DIO2-AS1 lnc-CEP128-7 lnc-CEP128-8
GH14J080387 Enhancer 0.8 Ensembl ENCODE 500.7 -1.6 -1644 4.8 EP300 TCF12 JUND TEAD4 FOS FOSL2 JUN NR3C1 GATA3 NFIB DIO2 piR-49400-029 DIO2-AS1
GH14J080458 Promoter 0.3 EPDnew 500.2 -70.8 -70810 0.1 DIO2 lnc-TSHR-3 piR-54488
GH14J080385 Enhancer 0.3 Ensembl 500.7 +1.8 1756 0.4 FOXA1 DIO2 lnc-CEP128-3 DIO2-AS1
GH14J080425 Enhancer 0.9 Ensembl ENCODE 10.7 -38.5 -38544 2.6 TCF12 JUND FOS EP300 SMARCC2 BRCA1 FOSL2 CEBPB CHD2 JUN DIO2 piR-54488 piR-49400-029 DIO2-AS1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around DIO2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for DIO2

Top Transcription factor binding sites by QIAGEN in the DIO2 gene promoter:
  • AP-1
  • deltaCREB

Genomic Locations for DIO2 Gene

Genomic Locations for DIO2 Gene
chr14:80,197,525-80,387,757
(GRCh38/hg38)
Size:
190,233 bases
Orientation:
Minus strand
chr14:80,663,868-80,854,100
(GRCh37/hg19)
Size:
190,233 bases
Orientation:
Minus strand

Genomic View for DIO2 Gene

Genes around DIO2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
DIO2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for DIO2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for DIO2 Gene

Proteins for DIO2 Gene

  • Protein details for DIO2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q92813-IOD2_HUMAN
    Recommended name:
    Type II iodothyronine deiodinase
    Protein Accession:
    Q92813
    Secondary Accessions:
    • B9EGK0
    • G3V315
    • Q6B0A3
    • Q9HCP7
    • Q9HCP8
    • Q9P1W4
    • Q9UDZ1

    Protein attributes for DIO2 Gene

    Size:
    273 amino acids
    Molecular mass:
    30552 Da
    Quaternary structure:
    • Interacts with USP20 and USP33. Interacts with MARCH6.
    Miscellaneous:
    • [Isoform 2]: Has a Sec in positions 90, 169 and 302.
    • [Isoform 3]: Has a Sec in position 37.
    SequenceCaution:
    • Sequence=AAC95470.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

    Alternative splice isoforms for DIO2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for DIO2 Gene

Selected DME Specific Peptides for DIO2 Gene

Q92813:
  • SFLLDAYKQVKLG
  • ADFLLVYI
  • RPLVVNFGS
  • FFSNCLFLALYDSV
  • NQEDRCAAA
  • VADFLLVYIDEAHP
  • YLGGKGPF
  • CHLLDFA
  • EAHPSDGW

Post-translational modifications for DIO2 Gene

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

Domains & Families for DIO2 Gene

Gene Families for DIO2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins
  • Predicted membrane proteins

Protein Domains for DIO2 Gene

Blocks:
  • Iodothyronine deiodinase, active site
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for DIO2 Gene

GenScript: Design optimal peptide antigens:
  • Type-II 5'-deiodinase (IOD2_HUMAN)
  • Type II iodothyronine deiodinase (Q9C0K2_HUMAN)
  • Type II iodothyronine deiodinase (Q9NZL0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q92813

UniProtKB/Swiss-Prot:

IOD2_HUMAN :
  • Belongs to the iodothyronine deiodinase family.
Family:
  • Belongs to the iodothyronine deiodinase family.
genes like me logo Genes that share domains with DIO2: view

Function for DIO2 Gene

Molecular function for DIO2 Gene

UniProtKB/Swiss-Prot Function:
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.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=3,3',5-triiodo-L-thyronine + A + H(+) + iodide = AH2 + L-thyroxine; Xref=Rhea:RHEA:19745, ChEBI:CHEBI:13193, ChEBI:CHEBI:15378, ChEBI:CHEBI:16382, ChEBI:CHEBI:17499, ChEBI:CHEBI:58448, ChEBI:CHEBI:533015; EC=1.21.99.4; Evidence=. ;.
GENATLAS Biochemistry:
iodothyronine 5'-deiodinase type II,selenocysteine containing,expressed in thyroid,involved in the regulation of local T4 to T3 conversion

Enzyme Numbers (IUBMB) for DIO2 Gene

Phenotypes From GWAS Catalog for DIO2 Gene

Gene Ontology (GO) - Molecular Function for DIO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004800 thyroxine 5'-deiodinase activity IEA,TAS 9837913
GO:0008430 selenium binding IC,TAS 9837913
GO:0016491 oxidoreductase activity IEA --
GO:0031625 ubiquitin protein ligase binding IPI 19651899
genes like me logo Genes that share ontologies with DIO2: view
genes like me logo Genes that share phenotypes with DIO2: view

Animal Models for DIO2 Gene

MGI Knock Outs for DIO2:

Animal Model Products

CRISPR Products

Clone Products

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for DIO2 Gene

Localization for DIO2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for DIO2 Gene

Membrane; Single-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for DIO2 gene
Compartment Confidence
plasma membrane 4
extracellular 3
mitochondrion 3
endoplasmic reticulum 3
cytoskeleton 2
peroxisome 2
nucleus 2
cytosol 2
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for DIO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005886 plasma membrane TAS --
GO:0016020 membrane IEA,IC 9837913
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with DIO2: view

Pathways & Interactions for DIO2 Gene

genes like me logo Genes that share pathways with DIO2: view

SIGNOR curated interactions for DIO2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for DIO2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001514 selenocysteine incorporation NAS 9837913
GO:0006590 thyroid hormone generation TAS 9837913
GO:0042403 thyroid hormone metabolic process IDA,IBA 19651899
GO:0042404 thyroid hormone catabolic process IEA --
GO:0042446 hormone biosynthetic process IEA --
genes like me logo Genes that share ontologies with DIO2: view

Drugs & Compounds for DIO2 Gene

(22) Drugs for DIO2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Levothyroxine Approved Pharma 0
Selenium Approved, Investigational, Vet_approved Pharma 226
Iodide Approved, Experimental Pharma 0
Liothyronine Approved, Vet_approved Pharma 0
Selenocysteine Experimental Pharma 0

(14) Additional Compounds for DIO2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Hydrogen Ion
  • H+
  • H(+)
  • Hydrogen cation
  • Hydron
  • Proton
I(-)
  • [HI]
  • HI
  • Hydriodic acid
  • Hydrogeniodid
  • Hydroiodic acid
Thyroxine sulfate
  • 3,5,3',5'-tetraiodo-L-Thyronine 4'-O-sulfate
  • 3,5,3',5'-tetraiodo-L-Thyronine 4'-O-sulphate
  • 3,5,3',5'-tetraiodo-L-Thyronine 4-O-sulfate
  • 3,5,3',5'-tetraiodo-L-Thyronine 4-O-sulphate
  • 3-[4-(4-Hydroxy-3,5-diiodophenoxy-4-O-sulfate)-3,5-diiodophenyl]-L-alanine
77074-49-8
genes like me logo Genes that share compounds with DIO2: view

Transcripts for DIO2 Gene

mRNA/cDNA for DIO2 Gene

6 REFSEQ mRNAs :
20 NCBI additional mRNA sequence :
11 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for DIO2 Gene

No ASD Table

Relevant External Links for DIO2 Gene

GeneLoc Exon Structure for
DIO2

Expression for DIO2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for DIO2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for DIO2 Gene

This gene is overexpressed in Esophagus - Mucosa (x7.4) and Thyroid (x7.0).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for DIO2

SOURCE GeneReport for Unigene cluster for DIO2 Gene:

Hs.202354

mRNA Expression by UniProt/SwissProt for DIO2 Gene:

Q92813-IOD2_HUMAN
Tissue specificity: Isoform 1 is expressed in the lung, trachea, kidney, heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain (PubMed:8755651, PubMed:11165050). Isoform 2 is expressed in the brain, heart, kidney and trachea (PubMed:11165050).

Evidence on tissue expression from TISSUES for DIO2 Gene

  • Lung(4.1)
  • Thyroid gland(4)
  • Nervous system(3)
  • Muscle(2)
genes like me logo Genes that share expression patterns with DIO2: view

No data available for Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for DIO2 Gene

Orthologs for DIO2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for DIO2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia DIO2 30
  • 99.68 (n)
dog
(Canis familiaris)
Mammalia DIO2 31 30
  • 93.58 (n)
OneToOne
cow
(Bos Taurus)
Mammalia DIO2 31 30
  • 92.13 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Dio2 17 31 30
  • 88.68 (n)
rat
(Rattus norvegicus)
Mammalia Dio2 30
  • 88.04 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia DIO2 31
  • 80 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia DIO2 31
  • 67 (a)
OneToOne
chicken
(Gallus gallus)
Aves DIO2 31 30
  • 77.27 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia DIO2 31
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia dio2 30
  • 73.57 (n)
African clawed frog
(Xenopus laevis)
Amphibia dio2-A 30
zebrafish
(Danio rerio)
Actinopterygii dio2 31 30 30
  • 70.82 (n)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.163 30
Species where no ortholog for DIO2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for DIO2 Gene

ENSEMBL:
Gene Tree for DIO2 (if available)
TreeFam:
Gene Tree for DIO2 (if available)

Paralogs for DIO2 Gene

Paralogs for DIO2 Gene

(2) SIMAP similar genes for DIO2 Gene using alignment to 8 proteins:

  • IOD2_HUMAN
  • A8K845_HUMAN
  • G3V2A7_HUMAN
  • G3V3A8_HUMAN
  • H0YJ42_HUMAN
  • H0YJQ8_HUMAN
  • Q9C0K2_HUMAN
  • Q9NZL0_HUMAN
genes like me logo Genes that share paralogs with DIO2: view

Variants for DIO2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for DIO2 Gene

SNP ID Clinical significance and condition Chr 14 pos Variation AA Info Type
787950 Benign: not provided 80,203,244(-) G/C NON_CODING_TRANSCRIPT_VARIANT,SYNONYMOUS_VARIANT
rs225014 - p.Thr92Ala
rs2839859 - p.Ala81Asp

Additional dbSNP identifiers (rs#s) for DIO2 Gene

Structural Variations from Database of Genomic Variants (DGV) for DIO2 Gene

Variant ID Type Subtype PubMed ID
esv25191 CNV gain 19812545
nsv1045241 CNV gain 25217958

Variation tolerance for DIO2 Gene

Residual Variation Intolerance Score: 45.7% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.80; 47.54% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for DIO2 Gene

Human Gene Mutation Database (HGMD)
DIO2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
DIO2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for DIO2 Gene

Disorders for DIO2 Gene

MalaCards: The human disease database

(13) MalaCards diseases for DIO2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
graves' disease
  • toxic diffuse goiter
euthyroid sick syndrome
  • sick-euthyroid syndrome
hypothyroidism
  • thyroid deficiency
thyroiditis
allan-herndon-dudley syndrome
  • ahds
- elite association - COSMIC cancer census association via MalaCards
Search DIO2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for DIO2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with DIO2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for DIO2 Gene

Publications for DIO2 Gene

  1. Association of genetic polymorphisms in the type II deiodinase gene with bipolar disorder in a subset of Chinese population. (PMID: 19427350) He B … Zhong N (Progress in neuro-psychopharmacology & biological psychiatry 2009) 3 23 41 54
  2. Type 2 deiodinase Thr92Ala polymorphism impact on clinical course and myocardial remodeling in patients with Graves' disease. (PMID: 19684474) Grineva E … Larionova V (Cell cycle (Georgetown, Tex.) 2009) 3 23 41 54
  3. Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. (PMID: 19190113) Panicker V … Dayan CM (The Journal of clinical endocrinology and metabolism 2009) 3 23 41 54
  4. The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase. (PMID: 19651899) Zavacki AM … Bianco AC (Molecular and cellular biology 2009) 3 4 23 54
  5. Studies of the common DIO2 Thr92Ala polymorphism and metabolic phenotypes in 7342 Danish white subjects. (PMID: 17077128) Grarup N … Pedersen O (The Journal of clinical endocrinology and metabolism 2007) 3 23 41 54

Products for DIO2 Gene

Sources for DIO2 Gene