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P55073 (IOD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Type III iodothyronine deiodinase

EC=1.97.1.11
Alternative name(s):
5DIII
DIOIII
Type 3 DI
Type-III 5'-deiodinase
Gene names
Name:DIO3
Synonyms:ITDI3, TXDI3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length278 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

3,3',5'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2.

Subunit structure

Homodimer. May undergo minor heretodimerization with DIO1 and DIO2. Ref.6

Subcellular location

Cell membrane; Single-pass type II membrane protein. Endosome membrane; Single-pass type II membrane protein Ref.5.

Tissue specificity

Expressed in placenta and several fetal tissues.

Sequence similarities

Belongs to the iodothyronine deiodinase family.

Biophysicochemical properties

Kinetic parameters:

KM=4.3 nM for Thyroxine Ref.4

Vmax=1.4 pmol/min/mg enzyme

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 278278Type III iodothyronine deiodinase
PRO_0000154323

Regions

Topological domain1 – 1616Cytoplasmic Potential
Transmembrane17 – 3620Helical; Signal-anchor for type II membrane protein; Potential
Topological domain37 – 278242Extracellular Potential

Sites

Active site1441

Amino acid modifications

Non-standard residue1441Selenocysteine

Experimental info

Mutagenesis1441U → A: Complete loss of activity. Ref.4
Sequence conflict31R → H in AAB35616. Ref.1
Sequence conflict531Q → K in AAB35616. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P55073 [UniParc].

Last modified February 26, 2008. Version 3.
Checksum: B16B0EE2B83C124C

FASTA27831,451
        10         20         30         40         50         60 
MLRSLLLHSL RLCAQTASCL VLFPRFLGTA FMLWLLDFLC IRKHFLGRRR RGQPEPEVEL 

        70         80         90        100        110        120 
NSEGEEVPPD DPPICVSDDN RLCTLASLKA VWHGQKLDFF KQAHEGGPAP NSEVVLPDGF 

       130        140        150        160        170        180 
QSQHILDYAQ GNRPLVLNFG SCTUPPFMAR MSAFQRLVTK YQRDVDFLII YIEEAHPSDG 

       190        200        210        220        230        240 
WVTTDSPYII PQHRSLEDRV SAARVLQQGA PGCALVLDTM ANSSSSAYGA YFERLYVIQS 

       250        260        270 
GTIMYQGGRG PDGYQVSELR TWLERYDEQL HGARPRRV 

« Hide

References

« Hide 'large scale' references
[1]"Type 3 iodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme."
Salvatore D., Low S.C., Berry M., Maia A.L., Harney J.W., Croteau W., St Germain D.L., Larsen P.R.
J. Clin. Invest. 96:2421-2430(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
Tissue: Placenta.
[2]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Duodenum.
[4]"Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference."
Kuiper G.G., Klootwijk W., Visser T.J.
Endocrinology 144:2505-2513(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF SEC-144, BIOPHYSICOCHEMICAL PROPERTIES.
[5]"Human type 3 iodothyronine selenodeiodinase is located in the plasma membrane and undergoes rapid internalization to endosomes."
Baqui M., Botero D., Gereben B., Curcio C., Harney J.W., Salvatore D., Sorimachi K., Larsen P.R., Bianco A.C.
J. Biol. Chem. 278:1206-1211(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[6]"The thyroid hormone-inactivating deiodinase functions as a homodimer."
Sagar G.D., Gereben B., Callebaut I., Mornon J.P., Zeold A., Curcio-Morelli C., Harney J.W., Luongo C., Mulcahey M.A., Larsen P.R., Huang S.A., Bianco A.C.
Mol. Endocrinol. 22:1382-1393(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
S79854 mRNA. Translation: AAB35616.2.
AL049836 Genomic DNA. No translation available.
BC017717 mRNA. Translation: AAH17717.2.
RefSeqNP_001353.4. NM_001362.3.
UniGeneHs.49322.

3D structure databases

ProteinModelPortalP55073.
SMRP55073. Positions 103-267.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108079. 3 interactions.
STRING9606.ENSP00000352273.

Chemistry

ChEMBLCHEMBL3611.

Polymorphism databases

DMDM172045679.

Proteomic databases

PaxDbP55073.
PRIDEP55073.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000359323; ENSP00000352273; ENSG00000197406.
GeneID1735.
KEGGhsa:1735.

Organism-specific databases

CTD1735.
GeneCardsGC14P102027.
HGNCHGNC:2885. DIO3.
MIM601038. gene.
neXtProtNX_P55073.
PharmGKBPA27339.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG297144.
HOGENOMHOG000007088.
HOVERGENHBG000099.
InParanoidP55073.
KOK07754.
OrthoDBEOG79PJQC.
PhylomeDBP55073.

Enzyme and pathway databases

BioCycMetaCyc:HS11928-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP55073.

Gene expression databases

CleanExHS_DIO3.
GenevestigatorP55073.

Family and domain databases

Gene3D3.40.30.10. 1 hit.
InterProIPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERPTHR11781. PTHR11781. 1 hit.
PfamPF00837. T4_deiodinase. 1 hit.
[Graphical view]
PIRSFPIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMSSF52833. SSF52833. 1 hit.
PROSITEPS01205. T4_DEIODINASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi1735.
NextBio7035.
PROP55073.
SOURCESearch...

Entry information

Entry nameIOD3_HUMAN
AccessionPrimary (citable) accession number: P55073
Secondary accession number(s): Q8WVN5
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 26, 2008
Last modified: April 16, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM