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Q92813 (IOD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length273 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 273273Type II iodothyronine deiodinase
PRO_0000154317

Regions

Transmembrane10 – 3425Helical; Potential

Sites

Active site1331

Amino acid modifications

Non-standard residue1331Selenocysteine
Non-standard residue2661Selenocysteine

Natural variations

Alternative sequence741Q → QLNCPPSGFSKDGHILCLVY EAYKSRLLVYSHLDLWM in isoform 2.
VSP_026154
Natural variant811A → D.
Corresponds to variant rs2839859 [ dbSNP | Ensembl ].
VAR_049640
Natural variant921T → A.
Corresponds to variant rs225014 [ dbSNP | Ensembl ].
VAR_047549

Experimental info

Sequence conflict1981L → P in BAB16838. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (hDII-a) [UniParc].

Last modified February 26, 2008. Version 4.
Checksum: 88D68B9AA6CB2A42

FASTA27330,552
        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 

« Hide

Isoform 2 (hDII-b) [UniParc].

Checksum: 9D9FC1EA33A4E5FB
Show »

FASTA30934,704

References

« Hide '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. 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].
[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.
RefSeqNP_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.
UniGeneHs.202354.
Hs.708526.
Hs.732170.

3D structure databases

ProteinModelPortalQ92813.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108078. 15 interactions.
STRING9606.ENSP00000373490.

Polymorphism databases

DMDM172045839.

Proteomic databases

PaxDbQ92813.
PRIDEQ92813.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000438257; ENSP00000405854; ENSG00000211448. [Q92813-1]
ENST00000557010; ENSP00000451419; ENSG00000211448. [Q92813-1]
GeneID1734.
KEGGhsa:1734.
UCSCuc010asy.3. human. [Q92813-1]
uc021rxa.1. human. [Q92813-2]

Organism-specific databases

CTD1734.
GeneCardsGC14M080663.
HGNCHGNC:2884. DIO2.
HPAHPA029544.
MIM601413. gene.
neXtProtNX_Q92813.
PharmGKBPA27338.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG146259.
HOGENOMHOG000007088.
HOVERGENHBG000099.
InParanoidQ92813.
KOK17904.
OrthoDBEOG7XPZ7H.
PhylomeDBQ92813.
TreeFamTF329721.

Enzyme and pathway databases

BioCycMetaCyc:HS00008-MONOMER.
BRENDA1.97.1.10. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ92813.

Gene expression databases

ArrayExpressQ92813.
BgeeQ92813.
CleanExHS_DIO2.
GenevestigatorQ92813.

Family and domain databases

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

Other

GeneWikiDIO2.
GenomeRNAi1734.
NextBio35516965.
PROQ92813.
SOURCESearch...

Entry information

Entry nameIOD2_HUMAN
AccessionPrimary (citable) accession number: Q92813
Secondary accession number(s): B9EGK0 expand/collapse secondary AC list , G3V315, Q6B0A3, Q9HCP8, Q9P1W4, Q9UDZ1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 26, 2008
Last modified: April 16, 2014
This is version 131 of the entry and version 4 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

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