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P49895

- IOD1_HUMAN

UniProt

P49895 - IOD1_HUMAN

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Protein

Type I iodothyronine deiodinase

Gene
DIO1, ITDI1, TXDI1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine). Plays a role in providing a source of plasma T3 by deiodination of T4 in peripheral tissues such as liver and kidney.

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei126 – 1261

GO - Molecular functioni

  1. selenium binding Source: ProtInc
  2. thyroxine 5'-deiodinase activity Source: ProtInc

GO - Biological processi

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

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Thyroid hormones biosynthesis

Enzyme and pathway databases

BRENDAi1.97.1.10. 2681.
ReactomeiREACT_15297. Regulation of thyroid hormone activity.
SABIO-RKP49895.

Names & Taxonomyi

Protein namesi
Recommended name:
Type I iodothyronine deiodinase (EC:1.97.1.10)
Alternative name(s):
5DI
DIOI
Type 1 DI
Type-I 5'-deiodinase
Gene namesi
Name:DIO1
Synonyms:ITDI1, TXDI1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:2883. DIO1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei13 – 3321Helical; Reviewed predictionAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

MIMi147892. gene+phenotype.
PharmGKBiPA27337.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 249249Type I iodothyronine deiodinasePRO_0000154311Add
BLAST

Proteomic databases

PaxDbiP49895.
PRIDEiP49895.

Expressioni

Gene expression databases

ArrayExpressiP49895.
BgeeiP49895.
GenevestigatoriP49895.

Structurei

3D structure databases

ProteinModelPortaliP49895.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG67608.
HOVERGENiHBG000099.
InParanoidiP49895.
KOiK01562.
OMAiRCNIWEF.
PhylomeDBiP49895.
TreeFamiTF329721.

Family and domain databases

Gene3Di3.40.30.10. 1 hit.
InterProiIPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view]
PANTHERiPTHR11781. PTHR11781. 1 hit.
PfamiPF00837. T4_deiodinase. 1 hit.
[Graphical view]
PIRSFiPIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMiSSF52833. SSF52833. 1 hit.
PROSITEiPS01205. T4_DEIODINASE. 1 hit.
[Graphical view]

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P49895-1) [UniParc]FASTAAdd to Basket

Also known as: 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

MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM    50
TRNPHFSHDN WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL 100
SGQRCNIWEF MQGNRPLVLN FGSCTUPSFM FKFDQFKRLI EDFSSIADFL 150
VIYIEEAHAS DGWAFKNNMD IRNHQNLQDR LQAAHLLLAR SPQCPVVVDT 200
MQNQSSQLYA ALPERLYIIQ EGRILYKGKS GPWNYNPEEV RAVLEKLHS 249
Length:249
Mass (Da):28,924
Last modified:February 26, 2008 - v3
Checksum:i2D8BBFBA54B5A927
GO
Isoform 2 (identifier: P49895-2) [UniParc]FASTAAdd to Basket

Also known as: b

The sequence of this isoform differs from the canonical sequence as follows:
     50-113: Missing.

Show »
Length:185
Mass (Da):21,252
Checksum:i91E53DDDFC99E838
GO
Isoform 3 (identifier: P49895-3) [UniParc]FASTAAdd to Basket

Also known as: c/f

The sequence of this isoform differs from the canonical sequence as follows:
     78-109: RWQRLEDTTELGGLAPNCPVVRLSGQRCNIWE → IGHWCUILEVVPDLHLCSNLTSSRGLLKTLVP
     110-249: Missing.

Note: The UGA codon in position 83 may either function as a selenocysteine codon or a translation termination codon.

Show »
Length:109
Mass (Da):12,581
Checksum:i11293D50D43993E9
GO
Isoform 4 (identifier: P49895-4) [UniParc]FASTAAdd to Basket

Also known as: d

The sequence of this isoform differs from the canonical sequence as follows:
     113-160: Missing.

Show »
Length:201
Mass (Da):23,390
Checksum:i04CBA7E9DFCC49FF
GO
Isoform 5 (identifier: P49895-5) [UniParc]FASTAAdd to Basket

Also known as: e

The sequence of this isoform differs from the canonical sequence as follows:
     161-161: D → G
     162-249: Missing.

Show »
Length:161
Mass (Da):18,712
Checksum:i925FC41D8C359953
GO
Isoform 6 (identifier: P49895-6) [UniParc]FASTAAdd to Basket

Also known as: k

The sequence of this isoform differs from the canonical sequence as follows:
     26-40: GKVLLILFPDRVKRN → APSISGSSURSVGSD
     41-249: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. The UGA codon in position 34 may either function as a selenocysteine codon or a translation termination codon.

Show »
Length:40
Mass (Da):4,292
Checksum:i0C907B0BF69B85FE
GO
Isoform 7 (identifier: P49895-7) [UniParc]FASTAAdd to Basket

Also known as: l

The sequence of this isoform differs from the canonical sequence as follows:
     114-249: Missing.

Show »
Length:113
Mass (Da):13,178
Checksum:i4C437DDA41E76153
GO
Isoform 8 (identifier: P49895-8) [UniParc]FASTAAdd to Basket

Also known as: m

The sequence of this isoform differs from the canonical sequence as follows:
     50-85: MTRNPHFSHDNWIPTFFSTQYFWFVLKVRWQRLEDT → PLAATRGHDUARGSGPKLPGGPPLRTEVQHLGVYAR
     86-249: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. The UGA codon in position 59 may either function as a selenocysteine codon or a translation termination codon.

Show »
Length:85
Mass (Da):9,270
Checksum:i3885B86A586951FC
GO
Isoform 9 (identifier: P49895-9) [UniParc]FASTAAdd to Basket

Also known as: s

The sequence of this isoform differs from the canonical sequence as follows:
     50-89: MTRNPHFSHD...QRLEDTTELG → PLAATRGHDU...LGVYARWLGF
     90-249: Missing.

Note: No experimental confirmation available. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. The UGA codon in position 59 may either function as a selenocysteine codon or a translation termination codon.

Show »
Length:89
Mass (Da):9,774
Checksum:i131E31116885B86A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei26 – 4015GKVLL…RVKRN → APSISGSSURSVGSD in isoform 6. VSP_012772Add
BLAST
Alternative sequencei41 – 249209Missing in isoform 6. VSP_012773Add
BLAST
Alternative sequencei50 – 11364Missing in isoform 2. VSP_012774Add
BLAST
Alternative sequencei50 – 8940MTRNP…TTELG → PLAATRGHDUARGSGPKLPG GPPLRTEVQHLGVYARWLGF in isoform 9. VSP_012779Add
BLAST
Alternative sequencei50 – 8536MTRNP…RLEDT → PLAATRGHDUARGSGPKLPG GPPLRTEVQHLGVYAR in isoform 8. VSP_012775Add
BLAST
Alternative sequencei78 – 10932RWQRL…CNIWE → IGHWCUILEVVPDLHLCSNL TSSRGLLKTLVP in isoform 3. VSP_012777Add
BLAST
Alternative sequencei86 – 249164Missing in isoform 8. VSP_012776Add
BLAST
Alternative sequencei90 – 249160Missing in isoform 9. VSP_012780Add
BLAST
Alternative sequencei110 – 249140Missing in isoform 3. VSP_012778Add
BLAST
Alternative sequencei113 – 16048Missing in isoform 4. VSP_012781Add
BLAST
Alternative sequencei114 – 249136Missing in isoform 7. VSP_012782Add
BLAST
Alternative sequencei161 – 1611D → G in isoform 5. VSP_012783
Alternative sequencei162 – 24988Missing in isoform 5. VSP_012784Add
BLAST

Non-standard residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-standard residuei126 – 1261Selenocysteine

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S48220 mRNA. Translation: AAB23670.2.
AY560374 mRNA. Translation: AAT02480.1.
AY560375 mRNA. Translation: AAT02481.1.
AY560376 mRNA. Translation: AAT02482.1.
AY560377 mRNA. Translation: AAT02483.1.
AY560378 mRNA. Translation: AAT02484.1.
AY560379 mRNA. Translation: AAT02485.1.
AY560380 mRNA. Translation: AAT02486.1.
AY560381 mRNA. Translation: AAT02487.1.
AY560382 mRNA. Translation: AAT02488.1.
AY560383 mRNA. Translation: AAT02489.1.
AL031427 Genomic DNA. No translation available.
BC017955 mRNA. Translation: AAH17955.2.
BC107170 mRNA. Translation: AAI07171.1.
BC107171 mRNA. Translation: AAI07172.1.
S79349 Genomic DNA. Translation: AAB35380.2.
CCDSiCCDS30722.1. [P49895-4]
CCDS41339.1. [P49895-1]
CCDS41340.1. [P49895-5]
CCDS53320.1. [P49895-2]
RefSeqiNP_000783.2. NM_000792.5. [P49895-1]
NP_001034804.1. NM_001039715.1. [P49895-4]
NP_001034805.1. NM_001039716.1. [P49895-5]
NP_998758.1. NM_213593.3. [P49895-2]
UniGeneiHs.251415.

Genome annotation databases

EnsembliENST00000322679; ENSP00000323198; ENSG00000211452. [P49895-5]
ENST00000361921; ENSP00000354643; ENSG00000211452. [P49895-1]
ENST00000388876; ENSP00000373528; ENSG00000211452. [P49895-4]
ENST00000525202; ENSP00000435725; ENSG00000211452. [P49895-2]
ENST00000532493; ENSP00000434758; ENSG00000211452. [P49895-7]
GeneIDi1733.
KEGGihsa:1733.
UCSCiuc001cwb.3. human. [P49895-4]
uc009vzl.3. human. [P49895-7]
uc021onp.1. human. [P49895-2]
uc021onq.1. human. [P49895-1]
uc021onr.1. human. [P49895-5]

Polymorphism databases

DMDMi182702125.

Keywords - Coding sequence diversityi

Alternative splicing, Selenocysteine

Cross-referencesi

Web resourcesi

Wikipedia

Deiodinase entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
S48220 mRNA. Translation: AAB23670.2 .
AY560374 mRNA. Translation: AAT02480.1 .
AY560375 mRNA. Translation: AAT02481.1 .
AY560376 mRNA. Translation: AAT02482.1 .
AY560377 mRNA. Translation: AAT02483.1 .
AY560378 mRNA. Translation: AAT02484.1 .
AY560379 mRNA. Translation: AAT02485.1 .
AY560380 mRNA. Translation: AAT02486.1 .
AY560381 mRNA. Translation: AAT02487.1 .
AY560382 mRNA. Translation: AAT02488.1 .
AY560383 mRNA. Translation: AAT02489.1 .
AL031427 Genomic DNA. No translation available.
BC017955 mRNA. Translation: AAH17955.2 .
BC107170 mRNA. Translation: AAI07171.1 .
BC107171 mRNA. Translation: AAI07172.1 .
S79349 Genomic DNA. Translation: AAB35380.2 .
CCDSi CCDS30722.1. [P49895-4 ]
CCDS41339.1. [P49895-1 ]
CCDS41340.1. [P49895-5 ]
CCDS53320.1. [P49895-2 ]
RefSeqi NP_000783.2. NM_000792.5. [P49895-1 ]
NP_001034804.1. NM_001039715.1. [P49895-4 ]
NP_001034805.1. NM_001039716.1. [P49895-5 ]
NP_998758.1. NM_213593.3. [P49895-2 ]
UniGenei Hs.251415.

3D structure databases

ProteinModelPortali P49895.
ModBasei Search...
MobiDBi Search...

Chemistry

ChEMBLi CHEMBL2019.

Polymorphism databases

DMDMi 182702125.

Proteomic databases

PaxDbi P49895.
PRIDEi P49895.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000322679 ; ENSP00000323198 ; ENSG00000211452 . [P49895-5 ]
ENST00000361921 ; ENSP00000354643 ; ENSG00000211452 . [P49895-1 ]
ENST00000388876 ; ENSP00000373528 ; ENSG00000211452 . [P49895-4 ]
ENST00000525202 ; ENSP00000435725 ; ENSG00000211452 . [P49895-2 ]
ENST00000532493 ; ENSP00000434758 ; ENSG00000211452 . [P49895-7 ]
GeneIDi 1733.
KEGGi hsa:1733.
UCSCi uc001cwb.3. human. [P49895-4 ]
uc009vzl.3. human. [P49895-7 ]
uc021onp.1. human. [P49895-2 ]
uc021onq.1. human. [P49895-1 ]
uc021onr.1. human. [P49895-5 ]

Organism-specific databases

CTDi 1733.
GeneCardsi GC01P054359.
HGNCi HGNC:2883. DIO1.
MIMi 147892. gene+phenotype.
neXtProti NX_P49895.
PharmGKBi PA27337.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG67608.
HOVERGENi HBG000099.
InParanoidi P49895.
KOi K01562.
OMAi RCNIWEF.
PhylomeDBi P49895.
TreeFami TF329721.

Enzyme and pathway databases

BRENDAi 1.97.1.10. 2681.
Reactomei REACT_15297. Regulation of thyroid hormone activity.
SABIO-RK P49895.

Miscellaneous databases

GenomeRNAii 1733.
NextBioi 7017.
PROi P49895.
SOURCEi Search...

Gene expression databases

ArrayExpressi P49895.
Bgeei P49895.
Genevestigatori P49895.

Family and domain databases

Gene3Di 3.40.30.10. 1 hit.
InterProi IPR000643. Iodothyronine_deiodinase.
IPR008261. Iodothyronine_deiodinase_AS.
IPR027252. Iodothyronine_deiodinase_I/III.
IPR012336. Thioredoxin-like_fold.
[Graphical view ]
PANTHERi PTHR11781. PTHR11781. 1 hit.
Pfami PF00837. T4_deiodinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF001330. IOD. 1 hit.
PIRSF500144. IODI_III. 1 hit.
SUPFAMi SSF52833. SSF52833. 1 hit.
PROSITEi PS01205. T4_DEIODINASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and in vitro expression of the human selenoprotein, type I iodothyronine deiodinase."
    Mandel S.J., Berry M.J., Kieffer J.D., Harney J.W., Warne R.L., Larsen P.R.
    J. Clin. Endocrinol. Metab. 75:1133-1139(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Type I iodothyronine deiodinase splice variants in human liver."
    Wassen F.J.W.S., Kuiper G.G.J.M., Visser T.J.
    Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 9).
    Tissue: Liver.
  3. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "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] (ISOFORMS 1 AND 5).
    Tissue: Kidney.
  5. "A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene."
    Toyoda N., Zavacki A.M., Maia A.L., Harney J.W., Larsen P.R.
    Mol. Cell. Biol. 15:5100-5112(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.

Entry informationi

Entry nameiIOD1_HUMAN
AccessioniPrimary (citable) accession number: P49895
Secondary accession number(s): Q1RN02
, Q3KNP8, Q6Q4C1, Q6Q4C2, Q6Q4C3, Q6Q4C4, Q6Q4C5, Q6Q4C6, Q6Q4C7, Q6Q4C9, Q8WWC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 26, 2008
Last modified: September 3, 2014
This is version 135 of the entry and version 3 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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