Seroatlas · Human Serome Atlas

DIO3

Thyroxine 5-deiodinase

Also known as: IOD3_HUMAN, TXDI3

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P55073
Gene
DIO3
Ensembl
ENSG00000197406
Chromosome
14
Canonical length
304 aa
Protein class
Enzymes, FDA approved drug targets, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location
Vesicles
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this intronless gene belongs to the iodothyronine deiodinase family. It catalyzes the inactivation of thyroid hormone by inner ring deiodination of the prohormone thyroxine (T4) and the bioactive hormone 3,3',5-triiodothyronine (T3) to inactive metabolites, 3,3',5'-triiodothyronine (RT3) and 3,3'-diiodothyronine (T2), respectively. This enzyme is highly expressed in pregnant uterus, placenta, fetal and neonatal tissues, and thought to prevent premature exposure of developing fetal tissues to adult levels of thyroid hormones. It regulates circulating fetal thyroid hormone concentrations, and thus plays a critical role in mammalian development. Knockout mice lacking this gene exhibit abnormalities related to development and reproduction, and increased activity of this enzyme in infants with hemangiomas causes severe hypothyroidism. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. Sec is encoded by the UGA codon, which 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. [provided by RefSeq, May 2016]

Canonical amino-acid sequenceUniProt

304 residues, UniProt reviewed canonical sequence.

>P55073|DIO3
     1  MPRQATSRLV VGEGEGSQGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP RFLGTAFMLW
    61  LLDFLCIRKH FLGRRRRGQP EPEVELNSEG EEVPPDDPPI CVSDDNRLCT LASLKAVWHG
   121  QKLDFFKQAH EGGPAPNSEV VLPDGFQSQH ILDYAQGNRP LVLNFGSCTU PPFMARMSAF
   181  QRLVTKYQRD VDFLIIYIEE AHPSDGWVTT DSPYIIPQHR SLEDRVSAAR VLQQGAPGCA
   241  LVLDTMANSS SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGAR
   301  PRRV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DIO3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Cell surface
Secreted
No
Transmembrane segments
1
Mean surface accessibility (rSASA)
0
Highest tissue expression
21 nTPM

Expression across tissuesHPA

Tissue

  • cervix: 21 nTPM
  • placenta: 18 nTPM
  • vagina: 15 nTPM
  • ovary: 13 nTPM
  • blood vessel: 8.3 nTPM
  • fallopian tube: 6.3 nTPM

Single-cell type

  • syncytiotrophoblasts: 104 nCPM
  • adipocytes: 47 nCPM
  • fibroblasts: 29 nCPM
  • leydig cells: 12 nCPM
  • myosatellite cells: 10 nCPM
  • decidual stromal cells: 9.5 nCPM

Immune cell

  • basophil: 0 nTPM
  • classical monocyte: 0 nTPM
  • eosinophil: 0 nTPM
  • gdT-cell: 0 nTPM
  • intermediate monocyte: 0 nTPM
  • MAIT T-cell: 0 nTPM

Brain region

  • thalamus: 7.9 nTPM
  • medulla oblongata: 2.9 nTPM
  • basal ganglia: 2.6 nTPM
  • cerebral cortex: 1.7 nTPM
  • amygdala: 0.9 nTPM
  • white matter: 0.9 nTPM

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
0.65
gnomAD pLI
0.62
gnomAD missense Z
1.97
DepMap mean gene effect
0.01
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads DIO3 as an antibody target. Whether an autoantibody or antibody against DIO3 could matter depends on whether native DIO3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

DIO3 is annotated at the cell surface, where native DIO3 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label DIO3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/DIO3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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