Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q92813

- IOD2_HUMAN

UniProt

Q92813 - IOD2_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein

Type II iodothyronine deiodinase

Gene

DIO2

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 T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.

Catalytic activityi

3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2.PROSITE-ProRule annotation

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei133 – 1331

GO - Molecular functioni

  1. selenium binding Source: UniProtKB
  2. thyroxine 5'-deiodinase activity Source: UniProtKB
  3. ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

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

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Thyroid hormones biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS00008-MONOMER.
BRENDAi1.97.1.10. 2681.
ReactomeiREACT_15297. Regulation of thyroid hormone activity.
SABIO-RKQ92813.

Names & Taxonomyi

Protein namesi
Recommended name:
Type II iodothyronine deiodinase (EC:1.97.1.10)
Alternative name(s):
5DII
DIOII
Type 2 DI
Type-II 5'-deiodinase
Gene namesi
Name:DIO2
Synonyms:ITDI2, TXDI2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 14

Organism-specific databases

HGNCiHGNC:2884. DIO2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei10 – 3425HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA27338.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 273273Type II iodothyronine deiodinasePRO_0000154317Add
BLAST

Post-translational modificationi

Ubiquitinated by MARCH6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33.2 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ92813.
PRIDEiQ92813.

Expressioni

Tissue specificityi

Heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain.

Gene expression databases

BgeeiQ92813.
CleanExiHS_DIO2.
ExpressionAtlasiQ92813. baseline and differential.
GenevestigatoriQ92813.

Organism-specific databases

HPAiHPA029544.

Interactioni

Subunit structurei

Interacts with USP20 and USP33. Interacts with MARCH6.2 Publications

Protein-protein interaction databases

BioGridi108078. 15 interactions.
STRINGi9606.ENSP00000373490.

Structurei

3D structure databases

ProteinModelPortaliQ92813.
SMRiQ92813. Positions 69-260.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the iodothyronine deiodinase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG146259.
GeneTreeiENSGT00730000110840.
HOGENOMiHOG000007088.
HOVERGENiHBG000099.
InParanoidiQ92813.
KOiK17904.
OrthoDBiEOG7XPZ7H.
PhylomeDBiQ92813.
TreeFamiTF329721.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11781. PTHR11781. 1 hit.
PfamiPF00837. T4_deiodinase. 1 hit.
[Graphical view]
PIRSFiPIRSF001330. IOD. 1 hit.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS01205. T4_DEIODINASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q92813-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGILSVDLLI TLQILPVFFS NCLFLALYDS VILLKHVVLL LSRSKSTRGE
60 70 80 90 100
WRRMLTSEGL RCVWKSFLLD AYKQVKLGED APNSSVVHVS STEGGDNSGN
110 120 130 140 150
GTQEKIAEGA TCHLLDFASP ERPLVVNFGS ATUPPFTSQL PAFRKLVEEF
160 170 180 190 200
SSVADFLLVY IDEAHPSDGW AIPGDSSLSF EVKKHQNQED RCAAAQQLLE
210 220 230 240 250
RFSLPPQCRV VADRMDNNAN IAYGVAFERV CIVQRQKIAY LGGKGPFSYN
260 270
LQEVRHWLEK NFSKRUKKTR LAG
Length:273
Mass (Da):30,552
Last modified:February 26, 2008 - v4
Checksum:i88D68B9AA6CB2A42
GO
Isoform 2 (identifier: Q92813-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:309
Mass (Da):34,704
Checksum:i9D9FC1EA33A4E5FB
GO

Sequence cautioni

The sequence AAC95470.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti198 – 1981L → P in BAB16838. (PubMed:11165050)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti81 – 811A → D.
Corresponds to variant rs2839859 [ dbSNP | Ensembl ].
VAR_049640
Natural varianti92 – 921T → A.
Corresponds to variant rs225014 [ dbSNP | Ensembl ].
VAR_047549

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei74 – 741Q → QLNCPPSGFSKDGHILCLVY EAYKSRLLVYSHLDLWM in isoform 2. 1 PublicationVSP_026154

Non-standard residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-standard residuei133 – 1331Selenocysteine
Non-standard residuei266 – 2661Selenocysteine

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS45146.1. [Q92813-1]
CCDS55934.1. [Q92813-2]
RefSeqiNP_000784.2. NM_000793.5. [Q92813-1]
NP_001007024.1. NM_001007023.3.
NP_001229431.1. NM_001242502.1.
NP_001229432.1. NM_001242503.1.
NP_054644.1. NM_013989.4. [Q92813-1]
UniGeneiHs.202354.
Hs.708526.
Hs.732170.

Genome annotation databases

EnsembliENST00000438257; ENSP00000405854; ENSG00000211448. [Q92813-1]
ENST00000557010; ENSP00000451419; ENSG00000211448. [Q92813-1]
GeneIDi1734.
KEGGihsa:1734.
UCSCiuc010asy.3. human. [Q92813-1]
uc021rxa.1. human. [Q92813-2]

Polymorphism databases

DMDMi172045839.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism, Selenocysteine

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 .
CCDSi CCDS45146.1. [Q92813-1 ]
CCDS55934.1. [Q92813-2 ]
RefSeqi NP_000784.2. NM_000793.5. [Q92813-1 ]
NP_001007024.1. NM_001007023.3.
NP_001229431.1. NM_001242502.1.
NP_001229432.1. NM_001242503.1.
NP_054644.1. NM_013989.4. [Q92813-1 ]
UniGenei Hs.202354.
Hs.708526.
Hs.732170.

3D structure databases

ProteinModelPortali Q92813.
SMRi Q92813. Positions 69-260.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108078. 15 interactions.
STRINGi 9606.ENSP00000373490.

Polymorphism databases

DMDMi 172045839.

Proteomic databases

PaxDbi Q92813.
PRIDEi Q92813.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000438257 ; ENSP00000405854 ; ENSG00000211448 . [Q92813-1 ]
ENST00000557010 ; ENSP00000451419 ; ENSG00000211448 . [Q92813-1 ]
GeneIDi 1734.
KEGGi hsa:1734.
UCSCi uc010asy.3. human. [Q92813-1 ]
uc021rxa.1. human. [Q92813-2 ]

Organism-specific databases

CTDi 1734.
GeneCardsi GC14M080663.
HGNCi HGNC:2884. DIO2.
HPAi HPA029544.
MIMi 601413. gene.
neXtProti NX_Q92813.
PharmGKBi PA27338.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG146259.
GeneTreei ENSGT00730000110840.
HOGENOMi HOG000007088.
HOVERGENi HBG000099.
InParanoidi Q92813.
KOi K17904.
OrthoDBi EOG7XPZ7H.
PhylomeDBi Q92813.
TreeFami TF329721.

Enzyme and pathway databases

BioCyci MetaCyc:HS00008-MONOMER.
BRENDAi 1.97.1.10. 2681.
Reactomei REACT_15297. Regulation of thyroid hormone activity.
SABIO-RK Q92813.

Miscellaneous databases

GeneWikii DIO2.
GenomeRNAii 1734.
NextBioi 35516965.
PROi Q92813.
SOURCEi Search...

Gene expression databases

Bgeei Q92813.
CleanExi HS_DIO2.
ExpressionAtlasi Q92813. baseline and differential.
Genevestigatori Q92813.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiIOD2_HUMAN
AccessioniPrimary (citable) accession number: Q92813
Secondary accession number(s): B9EGK0
, G3V315, Q6B0A3, Q9HCP8, Q9P1W4, Q9UDZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 26, 2008
Last modified: November 26, 2014
This is version 137 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3