DIO1

Protein identityUniProt · HPA

UniProt accession

P49895

Gene

DIO1

Ensembl

ENSG00000211452

Chromosome

1

Canonical length

249 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene belongs to the iodothyronine deiodinase family. It catalyzes the activation, as well as the inactivation of thyroid hormone by outer and inner ring deiodination, respectively. The activation reaction involves the conversion of the prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4), secreted by the thyroid gland, to the bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by 5'-deiodination. This protein provides most of the circulating T3, which is essential for growth, differentiation and basal metabolism in vertebrates. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2018]

Canonical amino-acid sequenceUniProt

249 residues, UniProt reviewed canonical sequence.

>P49895|DIO1
     1  MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN
    61  WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQGNRPLVLN
   121  FGSCTUPSFM FKFDQFKRLI EDFSSIADFL VIYIEEAHAS DGWAFKNNMD IRNHQNLQDR
   181  LQAAHLLLAR SPQCPVVVDT MQNQSSQLYA ALPERLYIIQ EGRILYKGKS GPWNYNPEEV
   241  RAVLEKLHS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DIO1 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

243 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DIO1.

Disease | AllUniProt

Conditions DIO1 is implicated in, by any mechanism.

• Thyroid hormone metabolism, abnormal, 2 (THMA2) MIM:619855

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 32 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Thyroid hormone metabolism, abnormal, 2

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)

0.56

gnomAD pLI

0.58

gnomAD missense Z

0.48

DepMap mean gene effect

0.05

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

• amino acid metabolic process
• hormone biosynthetic process
• thyroid hormone catabolic process
• thyroid hormone generation
• thyroid hormone metabolic process

Molecular functions

• selenium binding
• thyroxine 5'-deiodinase activity
• thyroxine 5-deiodinase activity

Cellular components

• basolateral plasma membrane
• endoplasmic reticulum membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Iodothyronine deiodinase
• Iodothyronine deiodinase, active site
• Iodothyronine deiodinase I/III
• Thioredoxin-like superfamily
• Iodothyronine deiodinase

KeywordsUniProt

• Cell membrane
• Endoplasmic reticulum
• Membrane
• Oxidoreductase
• Selenocysteine
• Thyroid hormones biosynthesis
• Transmembrane
• Transmembrane helix