P49895 (IOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Type I iodothyronine deiodinase
EC=1.97.1.10

Alternative name(s):
5DI
DIOI
Type 1 DI
Type-I 5'-deiodinase

Gene names

Name:	DIO1
Synonyms:	ITDI1, TXDI1

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	249 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	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 activity	3,5,3'-triiodo-L-thyronine + iodide + A + H+ = L-thyroxine + AH2.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein By similarity.
Sequence similarities	Belongs to the iodothyronine deiodinase family.

Ontologies

Keywords
Biological process	Thyroid hormones biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Selenocysteine
Domain	Transmembrane Transmembrane helix
Molecular function	Oxidoreductase
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 thyroid hormone generation Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	selenium binding Traceable author statement Ref.1. Source: ProtInc thyroxine 5'-deiodinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49895-1)

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.

Isoform 2 (identifier: P49895-2)

Also known as: b;

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

Isoform 3 (identifier: P49895-3)

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.

Isoform 4 (identifier: P49895-4)

Also known as: d;

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

Isoform 5 (identifier: P49895-5)

Also known as: e;

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

Isoform 6 (identifier: P49895-6)

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.

Isoform 7 (identifier: P49895-7)

Also known as: l;

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

Isoform 8 (identifier: P49895-8)

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.

Isoform 9 (identifier: P49895-9)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 249	249	Type I iodothyronine deiodinase		PRO_0000154311
Regions
	Transmembrane	13 – 33	21	Helical; Potential
Sites
	Active site	126	1
Amino acid modifications
	Non-standard residue	126	1	Selenocysteine
Natural variations
	Alternative sequence	26 – 40	15	GKVLL…RVKRN → APSISGSSURSVGSD in isoform 6.		VSP_012772
	Alternative sequence	41 – 249	209	Missing in isoform 6.		VSP_012773
	Alternative sequence	50 – 113	64	Missing in isoform 2.		VSP_012774
	Alternative sequence	50 – 89	40	MTRNP…TTELG → PLAATRGHDUARGSGPKLPG GPPLRTEVQHLGVYARWLGF in isoform 9.		VSP_012779
	Alternative sequence	50 – 85	36	MTRNP…RLEDT → PLAATRGHDUARGSGPKLPG GPPLRTEVQHLGVYAR in isoform 8.		VSP_012775
	Alternative sequence	78 – 109	32	RWQRL…CNIWE → IGHWCUILEVVPDLHLCSNL TSSRGLLKTLVP in isoform 3.		VSP_012777
	Alternative sequence	86 – 249	164	Missing in isoform 8.		VSP_012776
	Alternative sequence	90 – 249	160	Missing in isoform 9.		VSP_012780
	Alternative sequence	110 – 249	140	Missing in isoform 3.		VSP_012778
	Alternative sequence	113 – 160	48	Missing in isoform 4.		VSP_012781
	Alternative sequence	114 – 249	136	Missing in isoform 7.		VSP_012782
	Alternative sequence	161	1	D → G in isoform 5.		VSP_012783
	Alternative sequence	162 – 249	88	Missing in isoform 5.		VSP_012784

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (a) [UniParc]. Last modified February 26, 2008. Version 3. Checksum: 2D8BBFBA54B5A927	FASTA	249	28,924
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN 70 80 90 100 110 120 WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQGNRPLVLN 130 140 150 160 170 180 FGSCTUPSFM FKFDQFKRLI EDFSSIADFL VIYIEEAHAS DGWAFKNNMD IRNHQNLQDR 190 200 210 220 230 240 LQAAHLLLAR SPQCPVVVDT MQNQSSQLYA ALPERLYIIQ EGRILYKGKS GPWNYNPEEV RAVLEKLHS
	Isoform 2 (b) [UniParc]. Checksum: 91E53DDDFC99E838	FASTA	185	21,252
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGN RPLVLNFGSC 70 80 90 100 110 120 TUPSFMFKFD QFKRLIEDFS SIADFLVIYI EEAHASDGWA FKNNMDIRNH QNLQDRLQAA 130 140 150 160 170 180 HLLLARSPQC PVVVDTMQNQ SSQLYAALPE RLYIIQEGRI LYKGKSGPWN YNPEEVRAVL EKLHS
	Isoform 3 (c/f) [UniParc]. Checksum: 11293D50D43993E9	FASTA	109	12,581
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN 70 80 90 100 WIPTFFSTQY FWFVLKVIGH WCUILEVVPD LHLCSNLTSS RGLLKTLVP
	Isoform 4 (d) [UniParc]. Checksum: 04CBA7E9DFCC49FF	FASTA	201	23,390
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN 70 80 90 100 110 120 WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQDGWAFKNN 130 140 150 160 170 180 MDIRNHQNLQ DRLQAAHLLL ARSPQCPVVV DTMQNQSSQL YAALPERLYI IQEGRILYKG 190 200 KSGPWNYNPE EVRAVLEKLH S
	Isoform 5 (e) [UniParc]. Checksum: 925FC41D8C359953	FASTA	161	18,712
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN 70 80 90 100 110 120 WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQGNRPLVLN 130 140 150 160 FGSCTUPSFM FKFDQFKRLI EDFSSIADFL VIYIEEAHAS G
	Isoform 6 (k) [UniParc]. Checksum: 0C907B0BF69B85FE	FASTA	40	4,292
	10 20 30 40 MGLPQPGLWL KRLWVLLEVA VHVVVAPSIS GSSURSVGSD
	Isoform 7 (l) [UniParc]. Checksum: 4C437DDA41E76153	FASTA	113	13,178
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN 70 80 90 100 110 WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQG
	Isoform 8 (m) [UniParc]. Checksum: 3885B86A586951FC	FASTA	85	9,270
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGP LAATRGHDUA 70 80 RGSGPKLPGG PPLRTEVQHL GVYAR
	Isoform 9 (s) [UniParc]. Checksum: 131E31116885B86A	FASTA	89	9,774
	10 20 30 40 50 60 MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGP LAATRGHDUA 70 80 RGSGPKLPGG PPLRTEVQHL GVYARWLGF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Web resources

Wikipedia

Deiodinase entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00028634. IPI00412686. IPI00451418. IPI00451420. IPI00451421. IPI00514323. IPI00515078. IPI00552076. IPI00552688.
RefSeq	NP_000783.2. NM_000792.5. NP_001034804.1. NM_001039715.1. NP_001034805.1. NM_001039716.1. NP_998758.1. NM_213593.3.
UniGene	Hs.251415.
3D structure databases
ProteinModelPortal	P49895.
ModBase	Search...
Polymorphism databases
DMDM	182702125.
Proteomic databases
PaxDb	P49895.
PRIDE	P49895.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000322679; ENSP00000323198; ENSG00000211452. ENST00000361921; ENSP00000354643; ENSG00000211452. ENST00000388876; ENSP00000373528; ENSG00000211452. ENST00000525202; ENSP00000435725; ENSG00000211452. ENST00000532493; ENSP00000434758; ENSG00000211452.
GeneID	1733.
KEGG	hsa:1733.
UCSC	uc001cwb.3. human. uc009vzl.3. human. uc021onp.1. human. uc021onq.1. human. uc021onr.1. human.
Organism-specific databases
CTD	1733.
GeneCards	GC01P054359.
HGNC	HGNC:2883. DIO1.
MIM	147892. gene+phenotype.
neXtProt	NX_P49895.
PharmGKB	PA27337.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG67608.
HOVERGEN	HBG000099.
InParanoid	P49895.
KO	K01562.
OMA	NHQNLQD.
PhylomeDB	P49895.
Enzyme and pathway databases
BRENDA	1.97.1.10. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	P49895.
Gene expression databases
ArrayExpress	P49895.
Bgee	P49895.
Genevestigator	P49895.
GermOnline	ENSG00000181150. Homo sapiens. ENSG00000211452. Homo sapiens.
Family and domain databases
Gene3D	3.40.30.10. 1 hit.
InterPro	IPR000643. Iodothyronine_deiodinase. IPR008261. Iodothyronine_deiodinase_AS. IPR027252. Iodothyronine_deiodinase_I/III. IPR012336. Thioredoxin-like_fold. [Graphical view]
PANTHER	PTHR11781. PTHR11781. 1 hit.
Pfam	PF00837. T4_deiodinase. 1 hit. [Graphical view]
PIRSF	PIRSF001330. IOD. 1 hit. PIRSF500144. IODI_III. 1 hit.
PROSITE	PS01205. T4_DEIODINASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2019.
GenomeRNAi	1733.
NextBio	7017.
SOURCE	Search...

Entry information

Entry name

IOD1_HUMAN

Accession

Primary (citable) accession number: P49895
Secondary accession number(s): Q1RN02 , Q3KNP8, Q6Q4C1, Q6Q4C2, Q6Q4C3, Q6Q4C4, Q6Q4C5, Q6Q4C6, Q6Q4C7, Q6Q4C9, Q8WWC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 26, 2008
Last modified:	April 3, 2013
This is version 125 of the entry and version 3 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.