DIO2

Protein identityUniProt · HPA

UniProt accession

Q92813

Gene

DIO2

Ensembl

ENSG00000211448

Chromosome

14

Canonical length

273 aa

Protein class

Enzymes, Metabolic proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Vesicles,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

273 residues, UniProt reviewed canonical sequence.

>Q92813|DIO2
     1  MGILSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVVLL LSRSKSTRGE WRRMLTSEGL
    61  RCVWKSFLLD AYKQVKLGED APNSSVVHVS STEGGDNSGN GTQEKIAEGA TCHLLDFASP
   121  ERPLVVNFGS ATUPPFTSQL PAFRKLVEEF SSVADFLLVY IDEAHPSDGW AIPGDSSLSF
   181  EVKKHQNQED RCAAAQQLLE RFSLPPQCRV VADRMDNNAN IAYGVAFERV CIVQRQKIAY
   241  LGGKGPFSYN LQEVRHWLEK NFSKRUKKTR LAG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DIO2 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

Other membrane

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

333 nTPM

Expression across tissuesHPA

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)

0.54

gnomAD pLI

0.62

gnomAD missense Z

0.93

DepMap mean gene effect

0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• hormone biosynthetic process
• positive regulation of cold-induced thermogenesis
• response to lipopolysaccharide
• selenocysteine incorporation
• thyroid hormone catabolic process
• thyroid hormone generation
• thyroid hormone metabolic process

Molecular functions

• selenium binding
• thyroxine 5'-deiodinase activity
• thyroxine 5-deiodinase activity
• ubiquitin protein ligase binding

Cellular components

• endoplasmic reticulum membrane
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Iodothyronine deiodinase
• Iodothyronine deiodinase, active site
• Thioredoxin-like superfamily
• Iodothyronine deiodinase

KeywordsUniProt

• Endoplasmic reticulum
• Membrane
• Oxidoreductase
• Selenocysteine
• Thyroid hormones biosynthesis
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of DIO2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MARCHF6
• USP20
• USP33
• WSB1