Q92813 (IOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Type II iodothyronine deiodinase
EC=1.97.1.10

Alternative name(s):
5DII
DIOII
Type 2 DI
Type-II 5'-deiodinase

Gene names

Name:	DIO2
Synonyms:	ITDI2, TXDI2

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	273 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 T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.
Catalytic activity	3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2.
Subunit structure	Interacts with USP20 and USP33. Interacts with MARCH6. Ref.7 Ref.8
Subcellular location	Membrane; Single-pass membrane protein Potential.
Tissue specificity	Heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain.
Post-translational modification	Ubiquitinated by MARCH6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33. Ref.7 Ref.8
Sequence similarities	Belongs to the iodothyronine deiodinase family.
Sequence caution	The sequence AAC95470.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Thyroid hormones biosynthesis
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism Selenocysteine
Domain	Transmembrane Transmembrane helix
Molecular function	Oxidoreductase
PTM	Ubl conjugation
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 selenocysteine incorporation Non-traceable author statement Ref.2. Source: UniProtKB thyroid hormone generation Traceable author statement Ref.2. Source: UniProtKB
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	selenium binding Inferred by curator Ref.2. Source: UniProtKB thyroxine 5'-deiodinase activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92813-1)

Also known as: hDII-a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92813-2)

Also known as: hDII-b;

The sequence of this isoform differs from the canonical sequence as follows:
     74-74: Q → QLNCPPSGFSKDGHILCLVYEAYKSRLLVYSHLDLWM

Note: Has a Sec in positions 169 and 302.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 273	273	Type II iodothyronine deiodinase		PRO_0000154317
Regions
	Transmembrane	10 – 34	25	Helical; Potential
Sites
	Active site	133	1
Amino acid modifications
	Non-standard residue	133	1	Selenocysteine
	Non-standard residue	266	1	Selenocysteine
Natural variations
	Alternative sequence	74	1	Q → QLNCPPSGFSKDGHILCLVY EAYKSRLLVYSHLDLWM in isoform 2.		VSP_026154
	Natural variant	81	1	A → D. Corresponds to variant rs2839859 [ dbSNP | Ensembl ].		VAR_049640
	Natural variant	92	1	T → A. Corresponds to variant rs225014 [ dbSNP | Ensembl ].		VAR_047549
Experimental info
	Sequence conflict	198	1	L → P in BAB16838. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (hDII-a) [UniParc]. Last modified February 26, 2008. Version 4. Checksum: 88D68B9AA6CB2A42	FASTA	273	30,552
	10 20 30 40 50 60 MGILSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVVLL LSRSKSTRGE WRRMLTSEGL 70 80 90 100 110 120 RCVWKSFLLD AYKQVKLGED APNSSVVHVS STEGGDNSGN GTQEKIAEGA TCHLLDFASP 130 140 150 160 170 180 ERPLVVNFGS ATUPPFTSQL PAFRKLVEEF SSVADFLLVY IDEAHPSDGW AIPGDSSLSF 190 200 210 220 230 240 EVKKHQNQED RCAAAQQLLE RFSLPPQCRV VADRMDNNAN IAYGVAFERV CIVQRQKIAY 250 260 270 LGGKGPFSYN LQEVRHWLEK NFSKRUKKTR LAG
	Isoform 2 (hDII-b) [UniParc]. Checksum: 9D9FC1EA33A4E5FB	FASTA	309	34,704
	10 20 30 40 50 60 MGILSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVVLL LSRSKSTRGE WRRMLTSEGL 70 80 90 100 110 120 RCVWKSFLLD AYKQLNCPPS GFSKDGHILC LVYEAYKSRL LVYSHLDLWM VKLGEDAPNS 130 140 150 160 170 180 SVVHVSSTEG GDNSGNGTQE KIAEGATCHL LDFASPERPL VVNFGSATUP PFTSQLPAFR 190 200 210 220 230 240 KLVEEFSSVA DFLLVYIDEA HPSDGWAIPG DSSLSFEVKK HQNQEDRCAA AQQLLERFSL 250 260 270 280 290 300 PPQCRVVADR MDNNANIAYG VAFERVCIVQ RQKIAYLGGK GPFSYNLQEV RHWLEKNFSK RUKKTRLAG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues." Croteau W., Davey J.C., Galton V.A., St Germain D.L. J. Clin. Invest. 98:405-417(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"The 3'-untranslated region of human type 2 iodothyronine deiodinase mRNA contains a functional selenocysteine insertion sequence element." Buettner C., Harney J.W., Larsen P.R. J. Biol. Chem. 273:33374-33378(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Identification of two novel splicing variants of human type II iodothyronine deiodinase mRNA." Ohba K., Yoshioka T., Muraki T. Mol. Cell. Endocrinol. 172:169-175(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Umbilical vein.
[4]	"Sequencing of human chromosome 14q31 region." Dickhoff R., Madan A., Qin S., Abbasi N., Dors M., Rowen L., Harrison G., James R., Loretz C., Lasky S., Madan A., Prescott S., Ratcliffe A., Shaffer T., Hood L. Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"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].
[6]	"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] (ISOFORM 1). Tissue: Lung and Testis.
[7]	"Deubiquitination of type 2 iodothyronine deiodinase by von Hippel-Lindau protein-interacting deubiquitinating enzymes regulates thyroid hormone activation." Curcio-Morelli C., Zavacki A.M., Christofollete M., Gereben B., de Freitas B.C., Harney J.W., Li Z., Wu G., Bianco A.C. J. Clin. Invest. 112:189-196(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, DEUBIQUITINATION BY USP20 AND USP33, INTERACTION WITH USP20 AND USP33.
[8]	"The E3 ubiquitin ligase TEB4 mediates degradation of type 2 iodothyronine deiodinase." Zavacki A.M., Arrojo E Drigo R., Freitas B.C., Chung M., Harney J.W., Egri P., Wittmann G., Fekete C., Gereben B., Bianco A.C. Mol. Cell. Biol. 29:5339-5347(2009) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY MARCH6, INTERACTION WITH MARCH6.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U53506 mRNA. Translation: AAC50663.1. AF093774 mRNA. Translation: AAC95470.1. Different initiation. AB041843 mRNA. Translation: BAB16838.1. AC007372 Genomic DNA. Translation: AAD45494.1. AC010849 Genomic DNA. No translation available. AL049837 Genomic DNA. No translation available. BC074882 mRNA. Translation: AAH74882.1. BC136514 mRNA. Translation: AAI36515.1.
IPI	IPI00030716. IPI00465076.
RefSeq	NP_000784.2. NM_000793.5. NP_001007024.1. NM_001007023.3. NP_001229431.1. NM_001242502.1. NP_001229432.1. NM_001242503.1. NP_054644.1. NM_013989.4.
UniGene	Hs.202354. Hs.708526. Hs.732170.
3D structure databases
ProteinModelPortal	Q92813.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000373490.
Polymorphism databases
DMDM	172045839.
Proteomic databases
PaxDb	Q92813.
PRIDE	Q92813.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000438257; ENSP00000405854; ENSG00000211448. ENST00000557010; ENSP00000451419; ENSG00000211448.
GeneID	1734.
KEGG	hsa:1734.
UCSC	uc010asy.3. human. uc021rxa.1. human.
Organism-specific databases
CTD	1734.
GeneCards	GC14M080663.
HGNC	HGNC:2884. DIO2.
HPA	HPA029544.
MIM	601413. gene.
neXtProt	NX_Q92813.
PharmGKB	PA27338.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG146259.
HOGENOM	HOG000007088.
HOVERGEN	HBG000099.
InParanoid	Q92813.
KO	K01562.
Enzyme and pathway databases
BioCyc	MetaCyc:HS00008-MONOMER.
BRENDA	1.97.1.10. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q92813.
Gene expression databases
ArrayExpress	Q92813.
Bgee	Q92813.
CleanEx	HS_DIO2.
Genevestigator	Q92813.
GermOnline	ENSG00000211448. Homo sapiens.
Family and domain databases
Gene3D	3.40.30.10. 1 hit.
InterPro	IPR000643. Iodothyronine_deiodinase. IPR008261. Iodothyronine_deiodinase_AS. IPR012336. Thioredoxin-like_fold. [Graphical view]
PANTHER	PTHR11781. PTHR11781. 1 hit.
Pfam	PF00837. T4_deiodinase. 1 hit. [Graphical view]
PIRSF	PIRSF001330. IOD. 1 hit.
PROSITE	PS01205. T4_DEIODINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2054.
GenomeRNAi	1734.
NextBio	35516965.
SOURCE	Search...

Entry information

Entry name

IOD2_HUMAN

Accession

Primary (citable) accession number: Q92813
Secondary accession number(s): B9EGK0 , G3V315, Q6B0A3, Q9HCP8, Q9P1W4, Q9UDZ1

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 26, 2008
Last modified:	May 1, 2013
This is version 123 of the entry and version 4 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.