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P55073

- IOD3_HUMAN

UniProt

P55073 - IOD3_HUMAN

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Protein

Type III iodothyronine deiodinase

Gene
DIO3, ITDI3, TXDI3
Organism
Homo sapiens (Human)
Status
Reviewed - 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 + A + H+ = L-thyroxine + AH2.

Kineticsi

  1. KM=4.3 nM for Thyroxine1 Publication

Vmax=1.4 pmol/min/mg enzyme

Sites

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

GO - Molecular functioni

  1. thyroxine 5'-deiodinase activity Source: UniProtKB
  2. thyroxine 5-deiodinase activity Source: UniProtKB-EC

GO - Biological processi

  1. cellular nitrogen compound metabolic process Source: Reactome
  2. hormone biosynthetic process Source: UniProtKB-KW
  3. small molecule metabolic process Source: Reactome
  4. thyroid hormone generation Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Thyroid hormones biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS11928-MONOMER.
ReactomeiREACT_15297. Regulation of thyroid hormone activity.
SABIO-RKP55073.

Names & Taxonomyi

Protein namesi
Recommended name:
Type III iodothyronine deiodinase (EC:1.97.1.11)
Alternative name(s):
5DIII
DIOIII
Type 3 DI
Type-III 5'-deiodinase
Gene namesi
Name:DIO3
Synonyms:ITDI3, TXDI3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:2885. DIO3.

Subcellular locationi

Cell membrane; Single-pass type II membrane protein. Endosome membrane; Single-pass type II membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4444Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei45 – 6723Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini68 – 304237Extracellular Reviewed predictionAdd
BLAST

GO - Cellular componenti

  1. endosome membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi170 – 1701U → A: Complete loss of activity. 1 Publication

Organism-specific databases

PharmGKBiPA27339.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 304304Type III iodothyronine deiodinasePRO_0000154323Add
BLAST

Proteomic databases

PaxDbiP55073.
PRIDEiP55073.

Expressioni

Tissue specificityi

Expressed in placenta and several fetal tissues.

Gene expression databases

CleanExiHS_DIO3.
GenevestigatoriP55073.

Interactioni

Subunit structurei

Homodimer. May undergo minor heretodimerization with DIO1 and DIO2.1 Publication

Protein-protein interaction databases

BioGridi108079. 3 interactions.
STRINGi9606.ENSP00000352273.

Structurei

3D structure databases

ProteinModelPortaliP55073.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG297144.
HOGENOMiHOG000007088.
HOVERGENiHBG000099.
InParanoidiP55073.
KOiK07754.
OrthoDBiEOG79PJQC.
PhylomeDBiP55073.
TreeFamiTF329721.

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.

P55073-1 [UniParc]FASTAAdd to Basket

« Hide

MPRQATSRLV VGEGEGSQGA SGPAATMLRS LLLHSLRLCA QTASCLVLFP    50
RFLGTAFMLW LLDFLCIRKH FLGRRRRGQP EPEVELNSEG EEVPPDDPPI 100
CVSDDNRLCT LASLKAVWHG QKLDFFKQAH EGGPAPNSEV VLPDGFQSQH 150
ILDYAQGNRP LVLNFGSCTU PPFMARMSAF QRLVTKYQRD VDFLIIYIEE 200
AHPSDGWVTT DSPYIIPQHR SLEDRVSAAR VLQQGAPGCA LVLDTMANSS 250
SSAYGAYFER LYVIQSGTIM YQGGRGPDGY QVSELRTWLE RYDEQLHGAR 300
PRRV 304
Length:304
Mass (Da):33,947
Last modified:May 14, 2014 - v4
Checksum:i08B61835B353D3C7
GO

Sequence cautioni

The sequence AAB35616.2 differs from that shown. Reason: Frameshift at position 21.
The sequence AAH17717.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti29 – 291R → H in AAB35616. 1 Publication
Sequence conflicti79 – 791Q → K in AAB35616. 1 Publication

Non-standard residue

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S79854 mRNA. Translation: AAB35616.2. Frameshift.
AL049836 Genomic DNA. No translation available.
BC017717 mRNA. Translation: AAH17717.2. Different initiation.
CCDSiCCDS41992.2.
RefSeqiNP_001353.4. NM_001362.3.
UniGeneiHs.49322.

Genome annotation databases

EnsembliENST00000359323; ENSP00000352273; ENSG00000197406.
ENST00000510508; ENSP00000427336; ENSG00000197406.
GeneIDi1735.
KEGGihsa:1735.

Polymorphism databases

DMDMi172045679.

Keywords - Coding sequence diversityi

Selenocysteine

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S79854 mRNA. Translation: AAB35616.2 . Frameshift.
AL049836 Genomic DNA. No translation available.
BC017717 mRNA. Translation: AAH17717.2 . Different initiation.
CCDSi CCDS41992.2.
RefSeqi NP_001353.4. NM_001362.3.
UniGenei Hs.49322.

3D structure databases

ProteinModelPortali P55073.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108079. 3 interactions.
STRINGi 9606.ENSP00000352273.

Chemistry

ChEMBLi CHEMBL3611.

Polymorphism databases

DMDMi 172045679.

Proteomic databases

PaxDbi P55073.
PRIDEi P55073.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000359323 ; ENSP00000352273 ; ENSG00000197406 .
ENST00000510508 ; ENSP00000427336 ; ENSG00000197406 .
GeneIDi 1735.
KEGGi hsa:1735.

Organism-specific databases

CTDi 1735.
GeneCardsi GC14P102027.
HGNCi HGNC:2885. DIO3.
MIMi 601038. gene.
neXtProti NX_P55073.
PharmGKBi PA27339.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG297144.
HOGENOMi HOG000007088.
HOVERGENi HBG000099.
InParanoidi P55073.
KOi K07754.
OrthoDBi EOG79PJQC.
PhylomeDBi P55073.
TreeFami TF329721.

Enzyme and pathway databases

BioCyci MetaCyc:HS11928-MONOMER.
Reactomei REACT_15297. Regulation of thyroid hormone activity.
SABIO-RK P55073.

Miscellaneous databases

GenomeRNAii 1735.
NextBioi 35517882.
PROi P55073.
SOURCEi Search...

Gene expression databases

CleanExi HS_DIO3.
Genevestigatori P55073.

Family and domain databases

Gene3Di 3.40.30.10. 1 hit.
InterProi IPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view ]
PANTHERi PTHR11781. PTHR11781. 1 hit.
Pfami PF00837. T4_deiodinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMi SSF52833. SSF52833. 1 hit.
PROSITEi PS01205. T4_DEIODINASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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] OF 3-304.
    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-170, 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. Cited for: SUBUNIT.

Entry informationi

Entry nameiIOD3_HUMAN
AccessioniPrimary (citable) accession number: P55073
Secondary accession number(s): G3XAM0, Q8WVN5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 14, 2014
Last modified: September 3, 2014
This is version 138 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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