P55073 (IOD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	278 AA.
Sequence status	Complete.
Protein existence	Evidence 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

Ontologies

Keywords
Biological process	Thyroid hormones biosynthesis
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Selenocysteine
Domain	Signal-anchor Transmembrane Transmembrane helix
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW thyroid hormone generation Traceable author statement. Source: Reactome
Cellular_component	endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	thyroxine 5'-deiodinase activity Non-traceable author statement Ref.1. Source: UniProtKB thyroxine 5-deiodinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 278	278	Type III iodothyronine deiodinase		PRO_0000154323
Regions
	Topological domain	1 – 16	16	Cytoplasmic Potential
	Transmembrane	17 – 36	20	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	37 – 278	242	Extracellular Potential
Sites
	Active site	144	1
Amino acid modifications
	Non-standard residue	144	1	Selenocysteine
Experimental info
	Mutagenesis	144	1	U → A: Complete loss of activity. Ref.4
	Sequence conflict	3	1	R → H in AAB35616. Ref.1
	Sequence conflict	53	1	Q → K in AAB35616. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P55073 [UniParc]. Last modified February 26, 2008. Version 3. Checksum: B16B0EE2B83C124C	FASTA	278	31,451
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00296437.
RefSeq	NP_001353.4. NM_001362.3.
UniGene	Hs.49322.
3D structure databases
ProteinModelPortal	P55073.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000352273.
Polymorphism databases
DMDM	172045679.
Proteomic databases
PaxDb	P55073.
PRIDE	P55073.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000359323; ENSP00000352273; ENSG00000197406.
GeneID	1735.
KEGG	hsa:1735.
UCSC	uc021sdx.1. human.
Organism-specific databases
CTD	1735.
GeneCards	GC14P102027. GC14P102028.
HGNC	HGNC:2885. DIO3.
MIM	601038. gene.
neXtProt	NX_P55073.
PharmGKB	PA27339.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG297144.
HOGENOM	HOG000007088.
HOVERGEN	HBG000099.
InParanoid	P55073.
KO	K07754.
OrthoDB	EOG4X97HS.
Enzyme and pathway databases
BioCyc	MetaCyc:HS11928-MONOMER.
Reactome	REACT_111217. Metabolism.
SABIO-RK	P55073.
Gene expression databases
CleanEx	HS_DIO3.
Genevestigator	P55073.
Family and domain databases
Gene3D	3.40.30.10. 1 hit.
InterPro	IPR000643. Iodothyronine_deiodinase. IPR008261. Iodothyronine_deiodinase_AS. IPR027252. Iodothyronine_deiodinase_I/III. IPR012336. Thioredoxin-like_fold. [Graphical view]
PANTHER	PTHR11781. PTHR11781. 1 hit.
Pfam	PF00837. T4_deiodinase. 1 hit. [Graphical view]
PIRSF	PIRSF001330. IOD. 1 hit. PIRSF500144. IODI_III. 1 hit.
PROSITE	PS01205. T4_DEIODINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL3611.
GenomeRNAi	1735.
NextBio	7035.
SOURCE	Search...

Entry information

Entry name

IOD3_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.