IOD1_HUMAN
ID IOD1_HUMAN Reviewed; 249 AA.
AC P49895; Q1RN02; Q3KNP8; Q6Q4C1; Q6Q4C2; Q6Q4C3; Q6Q4C4; Q6Q4C5; Q6Q4C6;
AC Q6Q4C7; Q6Q4C9; Q8WWC6;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 3.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Type I iodothyronine deiodinase;
DE EC=1.21.99.4;
DE AltName: Full=5DI;
DE AltName: Full=DIOI;
DE AltName: Full=Type 1 DI;
DE AltName: Full=Type-I 5'-deiodinase;
GN Name=DIO1; Synonyms=ITDI1, TXDI1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1400883; DOI=10.1210/jcem.75.4.1400883;
RA Mandel S.J., Berry M.J., Kieffer J.D., Harney J.W., Warne R.L.,
RA Larsen P.R.;
RT "Cloning and in vitro expression of the human selenoprotein, type I
RT iodothyronine deiodinase.";
RL J. Clin. Endocrinol. Metab. 75:1133-1139(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8 AND 9).
RC TISSUE=Liver;
RA Wassen F.J.W.S., Kuiper G.G.J.M., Visser T.J.;
RT "Type I iodothyronine deiodinase splice variants in human liver.";
RL Submitted (FEB-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-25.
RX PubMed=7651427; DOI=10.1128/mcb.15.9.5100;
RA Toyoda N., Zavacki A.M., Maia A.L., Harney J.W., Larsen P.R.;
RT "A novel retinoid X receptor-independent thyroid hormone response element
RT is present in the human type 1 deiodinase gene.";
RL Mol. Cell. Biol. 15:5100-5112(1995).
CC -!- FUNCTION: Responsible for the deiodination of T4 (3,5,3',5'-
CC tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2
CC (3,3'-diiodothyronine). Plays a role in providing a source of plasma T3
CC by deiodination of T4 in peripheral tissues such as liver and kidney.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3,3',5-triiodo-L-thyronine + A + H(+) + iodide = AH2 + L-
CC thyroxine; Xref=Rhea:RHEA:19745, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16382, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:58448, ChEBI:CHEBI:533015; EC=1.21.99.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10107};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Single-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=9;
CC Name=1; Synonyms=a;
CC IsoId=P49895-1; Sequence=Displayed;
CC Name=2; Synonyms=b;
CC IsoId=P49895-2; Sequence=VSP_012774;
CC Name=3; Synonyms=c/f;
CC IsoId=P49895-3; Sequence=VSP_012777, VSP_012778;
CC Name=4; Synonyms=d;
CC IsoId=P49895-4; Sequence=VSP_012781;
CC Name=5; Synonyms=e;
CC IsoId=P49895-5; Sequence=VSP_012783, VSP_012784;
CC Name=6; Synonyms=k;
CC IsoId=P49895-6; Sequence=VSP_012772, VSP_012773;
CC Name=7; Synonyms=l;
CC IsoId=P49895-7; Sequence=VSP_012782;
CC Name=8; Synonyms=m;
CC IsoId=P49895-8; Sequence=VSP_012775, VSP_012776;
CC Name=9; Synonyms=s;
CC IsoId=P49895-9; Sequence=VSP_012779, VSP_012780;
CC -!- MISCELLANEOUS: [Isoform 3]: The UGA codon in position 83 may either
CC function as a selenocysteine codon or a translation termination codon.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. The UGA codon in position 34 may either function as a
CC selenocysteine codon or a translation termination codon. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 8]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. The UGA codon in position 59 may either function as a
CC selenocysteine codon or a translation termination codon. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 9]: May be produced at very low levels due to a
CC premature stop codon in the mRNA, leading to nonsense-mediated mRNA
CC decay. The UGA codon in position 59 may either function as a
CC selenocysteine codon or a translation termination codon. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the iodothyronine deiodinase family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Deiodinase entry;
CC URL="https://en.wikipedia.org/wiki/Deiodinase";
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DR EMBL; S48220; AAB23670.2; -; mRNA.
DR EMBL; AY560374; AAT02480.1; -; mRNA.
DR EMBL; AY560375; AAT02481.1; -; mRNA.
DR EMBL; AY560376; AAT02482.1; -; mRNA.
DR EMBL; AY560377; AAT02483.1; -; mRNA.
DR EMBL; AY560378; AAT02484.1; -; mRNA.
DR EMBL; AY560379; AAT02485.1; -; mRNA.
DR EMBL; AY560380; AAT02486.1; -; mRNA.
DR EMBL; AY560381; AAT02487.1; -; mRNA.
DR EMBL; AY560382; AAT02488.1; -; mRNA.
DR EMBL; AY560383; AAT02489.1; -; mRNA.
DR EMBL; AL031427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017955; AAH17955.2; -; mRNA.
DR EMBL; BC107170; AAI07171.1; -; mRNA.
DR EMBL; BC107171; AAI07172.1; -; mRNA.
DR EMBL; S79349; AAB35380.2; -; Genomic_DNA.
DR CCDS; CCDS30722.1; -. [P49895-4]
DR CCDS; CCDS41339.1; -. [P49895-1]
DR CCDS; CCDS41340.1; -. [P49895-5]
DR CCDS; CCDS53320.1; -. [P49895-2]
DR CCDS; CCDS81328.1; -. [P49895-7]
DR RefSeq; NP_000783.2; NM_000792.6. [P49895-1]
DR RefSeq; NP_001034804.1; NM_001039715.2. [P49895-4]
DR RefSeq; NP_001034805.1; NM_001039716.2. [P49895-5]
DR RefSeq; NP_001311245.1; NM_001324316.1. [P49895-7]
DR RefSeq; NP_998758.1; NM_213593.4. [P49895-2]
DR BioGRID; 108077; 1.
DR STRING; 9606.ENSP00000354643; -.
DR ChEMBL; CHEMBL2019; -.
DR DrugBank; DB09100; Thyroid, porcine.
DR DrugCentral; P49895; -.
DR iPTMnet; P49895; -.
DR PhosphoSitePlus; P49895; -.
DR BioMuta; DIO1; -.
DR DMDM; 182702125; -.
DR EPD; P49895; -.
DR MassIVE; P49895; -.
DR PaxDb; P49895; -.
DR PeptideAtlas; P49895; -.
DR PRIDE; P49895; -.
DR ProteomicsDB; 56164; -. [P49895-1]
DR ProteomicsDB; 56165; -. [P49895-2]
DR ProteomicsDB; 56166; -. [P49895-3]
DR ProteomicsDB; 56167; -. [P49895-4]
DR ProteomicsDB; 56168; -. [P49895-5]
DR ProteomicsDB; 56170; -. [P49895-7]
DR ProteomicsDB; 56171; -. [P49895-8]
DR ProteomicsDB; 56172; -. [P49895-9]
DR Antibodypedia; 33120; 124 antibodies from 26 providers.
DR DNASU; 1733; -.
DR Ensembl; ENST00000322679.10; ENSP00000323198.6; ENSG00000211452.12. [P49895-5]
DR Ensembl; ENST00000361921.8; ENSP00000354643.4; ENSG00000211452.12. [P49895-1]
DR Ensembl; ENST00000388876.3; ENSP00000373528.3; ENSG00000211452.12. [P49895-4]
DR Ensembl; ENST00000525202.5; ENSP00000435725.1; ENSG00000211452.12. [P49895-2]
DR Ensembl; ENST00000532493.5; ENSP00000434758.1; ENSG00000211452.12. [P49895-7]
DR GeneID; 1733; -.
DR KEGG; hsa:1733; -.
DR MANE-Select; ENST00000361921.8; ENSP00000354643.4; NM_000792.7; NP_000783.2.
DR UCSC; uc001cwb.4; human. [P49895-1]
DR CTD; 1733; -.
DR DisGeNET; 1733; -.
DR GeneCards; DIO1; -.
DR HGNC; HGNC:2883; DIO1.
DR HPA; ENSG00000211452; Group enriched (kidney, liver, thyroid gland).
DR MIM; 147892; gene+phenotype.
DR neXtProt; NX_P49895; -.
DR OpenTargets; ENSG00000211452; -.
DR PharmGKB; PA27337; -.
DR VEuPathDB; HostDB:ENSG00000211452; -.
DR eggNOG; ENOG502QUGZ; Eukaryota.
DR GeneTree; ENSGT00940000154482; -.
DR HOGENOM; CLU_089345_2_0_1; -.
DR InParanoid; P49895; -.
DR OMA; SFGSCTX; -.
DR PhylomeDB; P49895; -.
DR TreeFam; TF329721; -.
DR BRENDA; 1.21.99.4; 2681.
DR PathwayCommons; P49895; -.
DR Reactome; R-HSA-350864; Regulation of thyroid hormone activity.
DR SABIO-RK; P49895; -.
DR SIGNOR; P49895; -.
DR BioGRID-ORCS; 1733; 7 hits in 1063 CRISPR screens.
DR ChiTaRS; DIO1; human.
DR GenomeRNAi; 1733; -.
DR Pharos; P49895; Tclin.
DR PRO; PR:P49895; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P49895; protein.
DR Bgee; ENSG00000211452; Expressed in right lobe of thyroid gland and 107 other tissues.
DR ExpressionAtlas; P49895; baseline and differential.
DR Genevisible; P49895; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0008430; F:selenium binding; TAS:ProtInc.
DR GO; GO:0004800; F:thyroxine 5'-deiodinase activity; IBA:GO_Central.
DR GO; GO:0006520; P:cellular amino acid metabolic process; IGI:ARUK-UCL.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006590; P:thyroid hormone generation; TAS:ProtInc.
DR GO; GO:0042403; P:thyroid hormone metabolic process; IBA:GO_Central.
DR InterPro; IPR000643; Iodothyronine_deiodinase.
DR InterPro; IPR008261; Iodothyronine_deiodinase_AS.
DR InterPro; IPR027252; Iodothyronine_deiodinase_I/III.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR PANTHER; PTHR11781; PTHR11781; 1.
DR Pfam; PF00837; T4_deiodinase; 1.
DR PIRSF; PIRSF001330; IOD; 1.
DR PIRSF; PIRSF500144; IODI_III; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS01205; T4_DEIODINASE; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Endoplasmic reticulum; Membrane; Oxidoreductase;
KW Reference proteome; Selenocysteine; Thyroid hormones biosynthesis;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..249
FT /note="Type I iodothyronine deiodinase"
FT /id="PRO_0000154311"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT ACT_SITE 126
FT NON_STD 126
FT /note="Selenocysteine"
FT VAR_SEQ 26..40
FT /note="GKVLLILFPDRVKRN -> APSISGSSURSVGSD (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012772"
FT VAR_SEQ 41..249
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012773"
FT VAR_SEQ 50..113
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012774"
FT VAR_SEQ 50..89
FT /note="MTRNPHFSHDNWIPTFFSTQYFWFVLKVRWQRLEDTTELG -> PLAATRGH
FT DUARGSGPKLPGGPPLRTEVQHLGVYARWLGF (in isoform 9)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012779"
FT VAR_SEQ 50..85
FT /note="MTRNPHFSHDNWIPTFFSTQYFWFVLKVRWQRLEDT -> PLAATRGHDUAR
FT GSGPKLPGGPPLRTEVQHLGVYAR (in isoform 8)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012775"
FT VAR_SEQ 78..109
FT /note="RWQRLEDTTELGGLAPNCPVVRLSGQRCNIWE -> IGHWCUILEVVPDLHL
FT CSNLTSSRGLLKTLVP (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012777"
FT VAR_SEQ 86..249
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012776"
FT VAR_SEQ 90..249
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012780"
FT VAR_SEQ 110..249
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012778"
FT VAR_SEQ 113..160
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012781"
FT VAR_SEQ 114..249
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_012782"
FT VAR_SEQ 161
FT /note="D -> G (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_012783"
FT VAR_SEQ 162..249
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_012784"
SQ SEQUENCE 249 AA; 28924 MW; 2D8BBFBA54B5A927 CRC64;
MGLPQPGLWL KRLWVLLEVA VHVVVGKVLL ILFPDRVKRN ILAMGEKTGM TRNPHFSHDN
WIPTFFSTQY FWFVLKVRWQ RLEDTTELGG LAPNCPVVRL SGQRCNIWEF MQGNRPLVLN
FGSCTUPSFM FKFDQFKRLI EDFSSIADFL VIYIEEAHAS DGWAFKNNMD IRNHQNLQDR
LQAAHLLLAR SPQCPVVVDT MQNQSSQLYA ALPERLYIIQ EGRILYKGKS GPWNYNPEEV
RAVLEKLHS
