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Protein

Thyroxine 5-deiodinase

Gene

Dio3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine). RT3 and T2 are inactive metabolites. May play a role in preventing premature exposure of developing fetal tissues to adult levels of thyroid hormones. Can regulate circulating fetal thyroid hormone concentrations throughout gestation. Essential role for regulation of thyroid hormone inactivation during embryological development.1 Publication

Catalytic activityi

3,3',5'-triiodo-L-thyronine + iodide + acceptor + H+ = L-thyroxine + reduced acceptor.1 Publication

Kineticsi

The Kcat/KM ratio for 5 deiodination of T3 is over 1'000-fold that of 5'-deiodination of reverse T3.1 Publication

  1. KM=1.25 µM for 3,5-diiodo-L-thyronine1 Publication
  1. Vmax=25 pmol/min/mg enzyme towards 3-iodo-L-thyronine1 Publication

pH dependencei

Optimum pH is 8.3.1 Publication

Temperature dependencei

Optimum temperature is 37 degrees Celsius.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei170 – 1701

GO - Molecular functioni

  • thyroxine 5'-deiodinase activity Source: RGD

GO - Biological processi

  • brown fat cell proliferation Source: RGD
  • hormone biosynthetic process Source: UniProtKB-KW
  • response to hypoxia Source: RGD
  • thyroid hormone metabolic process Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Thyroid hormones biosynthesis

Enzyme and pathway databases

BRENDAi1.97.1.11. 5301.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroxine 5-deiodinase (EC:1.21.99.31 Publication)
Alternative name(s):
5DIII
DIOIII
Type 3 DI
Type III iodothyronine deiodinase
Gene namesi
Name:Dio3
Synonyms:Itdi3, Txdi3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68420. Dio3.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4242CytoplasmicSequence analysisAdd
BLAST
Transmembranei43 – 6220Helical; Signal-anchor for type II membrane proteinSequence analysisAdd
BLAST
Topological domaini63 – 304242ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi170 – 1701U → L: Loss of enzyme activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 304304Thyroxine 5-deiodinasePRO_0000154325Add
BLAST

PTM databases

PhosphoSiteiP49897.

Expressioni

Tissue specificityi

Neonatal skin, placenta, skeletal muscle and cerebral cortex.1 Publication

Interactioni

Subunit structurei

Homodimer. May undergo minor heretodimerization with DIO1 and DIO2.By similarity

Family & Domainsi

Sequence similaritiesi

Belongs to the iodothyronine deiodinase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG000099.
InParanoidiP49897.
KOiK07754.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11781. PTHR11781. 1 hit.
PfamiPF00837. T4_deiodinase. 1 hit.
[Graphical view]
PIRSFiPIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS01205. T4_DEIODINASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P49897-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRQAASRLV VGEGEGPPGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP
60 70 80 90 100
RFLGTAFMLW LLDFLCIRKH FLRRRHPDHP EPEVELNSEG EEMPPDDPPI
110 120 130 140 150
CVSDDNRLCT LASLKAVWHG QKLDFFKQAH EGGPAPNSEV VRPDGFQSQR
160 170 180 190 200
ILDYAQGTRP LVLNFGSCTU PPFMARMSAF QRLVTKYQRD VDFLIIYIEE
210 220 230 240 250
AHPSDGWVTT DSPYVIPQHR SLEDRVSAAR VLQQGAPGCA LVLDTMANSS
260 270 280 290 300
SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGTR

PRRL
Length:304
Mass (Da):34,096
Last modified:May 14, 2014 - v3
Checksum:i899DC2E9B4104A15
GO

Sequence cautioni

The sequence AAC52241 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Non-standard residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-standard residuei170 – 1701Selenocysteine

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06046288 Genomic DNA. No translation available.
U24282 mRNA. Translation: AAC52241.2. Different initiation.
PIRiA57240.
RefSeqiNP_058906.3. NM_017210.3.
UniGeneiRn.11237.

Genome annotation databases

GeneIDi29475.
KEGGirno:29475.

Keywords - Coding sequence diversityi

Selenocysteine

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR06046288 Genomic DNA. No translation available.
U24282 mRNA. Translation: AAC52241.2. Different initiation.
PIRiA57240.
RefSeqiNP_058906.3. NM_017210.3.
UniGeneiRn.11237.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiP49897.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29475.
KEGGirno:29475.

Organism-specific databases

CTDi1735.
RGDi68420. Dio3.

Phylogenomic databases

HOVERGENiHBG000099.
InParanoidiP49897.
KOiK07754.

Enzyme and pathway databases

BRENDAi1.97.1.11. 5301.

Miscellaneous databases

PROiP49897.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11781. PTHR11781. 1 hit.
PfamiPF00837. T4_deiodinase. 1 hit.
[Graphical view]
PIRSFiPIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS01205. T4_DEIODINASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIOD3_RAT
AccessioniPrimary (citable) accession number: P49897
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 14, 2014
Last modified: September 7, 2016
This is version 116 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-27 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.