P70551 (IOD2_RAT) 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

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	266 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Catalyzes 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 By similarity.
Subcellular location	Membrane; Single-pass membrane protein Potential.
Tissue specificity	Expressed in cerebral cortex, cerebellum, pituitary gland, mostly in anterior pituitary gland, and pineal gland, as well as in brown adipose tissue (BAT). Ref.1 Ref.3 Ref.4
Induction	In the pineal gland, exhibits night/day variations with a 9-fold increased expression at night. Up-regulation is due to a large degree to the release of norepinephrine from nerve terminals in the pineal gland and cAMP signaling pathway. In BAT, up-regulated in animals exposed to cold. Ref.1 Ref.3 Ref.4
Post-translational modification	Ubiquitinated by MARCH6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33 By similarity.
Sequence similarities	Belongs to the iodothyronine deiodinase family.

Ontologies

Keywords
Biological process	Thyroid hormones biosynthesis
Cellular component	Membrane
Coding sequence diversity	Selenocysteine
Domain	Transmembrane Transmembrane helix
Molecular function	Oxidoreductase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	hormone biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW response to cold Inferred from direct assay PubMed 11934678. Source: RGD response to lipopolysaccharide Inferred from expression pattern PubMed 16095572. Source: RGD thyroid hormone generation Inferred from direct assay PubMed 15550511. Source: RGD
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	thyroxine 5'-deiodinase activity Inferred from direct assay PubMed 11934678PubMed 15550511. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 266	266	Type II iodothyronine deiodinase		PRO_0000154319
Regions
	Transmembrane	10 – 34	25	Helical; Potential
Sites
	Active site	130	1
Amino acid modifications
	Non-standard residue	130	1	Selenocysteine
	Non-standard residue	263	1	Selenocysteine
Experimental info
	Sequence conflict	116	1	S → C in BAA25186. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P70551 [UniParc]. Last modified February 26, 2008. Version 4. Checksum: 06DE3292FB467578	FASTA	266	29,871
	10 20 30 40 50 60 MGLLSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVALL LSRSKSTRGE WRRMLTSEGL 70 80 90 100 110 120 RCVWNSFLLD AYKQVKLGED APNSSVVHVS NPEAGNNCAS EKTADGAECH LLDFASAERP 130 140 150 160 170 180 LVVNFGSATU PPFTRQLPAF RQLVEEFSSV ADFLLVYIDE AHPSDGWAVP GDSSMSFEVK 190 200 210 220 230 240 KHRNQEDRCA AAHQLLERFS LPPQCQVVAD RMDNNANVAY GVAFERVCIV QRRKIAYLGG 250 260 KGPFSYNLQE VRSWLEKNFS KRUILD

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], TISSUE SPECIFICITY, INDUCTION. Strain: Sprague-Dawley. Tissue: Brown adipose tissue.
[2]	"Induction of type 2 deiodinase activity by cyclic guanosine 3',5'-monophosphate in cultured rat glial cells." Gondou A., Toyoda N., Nishikawa M., Tabata S., Yonemoto T., Ogawa Y., Tokoro T., Sakaguchi N., Wang F., Inada M. Thyroid 8:615-622(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Expression and nocturnal increase of type II iodothyronine deiodinase mRNA in rat pineal gland." Murakami M., Hosoi Y., Negishi T., Kamiya Y., Ogiwara T., Mizuma H., Yamada M., Iriuchijima T., Mori M. Neurosci. Lett. 227:65-67(1997) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
[4]	"Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling." Bailey M.J., Coon S.L., Carter D.A., Humphries A., Kim J.S., Shi Q., Gaildrat P., Morin F., Ganguly S., Hogenesch J.B., Weller J.L., Rath M.F., Moller M., Baler R., Sugden D., Rangel Z.G., Munson P.J., Klein D.C. J. Biol. Chem. 284:7606-7622(2009) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U53505 mRNA. Translation: AAC52767.1. AB011068 mRNA. Translation: BAA25186.1.
IPI	IPI00189693.
PIR	T10816.
RefSeq	NP_113908.3. NM_031720.3.
UniGene	Rn.88380.
3D structure databases
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	65162.
KEGG	rno:65162.
UCSC	RGD:68418. rat.
Organism-specific databases
CTD	1734.
RGD	68418. Dio2.
Phylogenomic databases
eggNOG	NOG146259.
HOGENOM	HOG000007088.
HOVERGEN	HBG000099.
InParanoid	P70551.
KO	K01562.
OrthoDB	EOG4X97HS.
Gene expression databases
Genevestigator	P70551.
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]
PROSITE	PS01205. T4_DEIODINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	614031.

Entry information

Entry name

IOD2_RAT

Accession

Primary (citable) accession number: P70551
Secondary accession number(s): O70179

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	February 26, 2008
Last modified:	April 3, 2013
This is version 103 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program