IYD1_HUMAN
ID IYD1_HUMAN Reviewed; 289 AA.
AC Q6PHW0; C9JFW2; Q2VPW0; Q2VPW1; Q5F1L5; Q5F1L6; Q5THM4; Q6ZP69; Q7Z7D7;
AC Q7Z7D8;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Iodotyrosine deiodinase 1 {ECO:0000303|PubMed:25395621};
DE Short=IYD-1 {ECO:0000303|PubMed:25395621};
DE EC=1.21.1.1 {ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
DE AltName: Full=Iodotyrosine dehalogenase 1 {ECO:0000303|PubMed:15289438, ECO:0000303|Ref.2};
GN Name=IYD {ECO:0000303|PubMed:25395621};
GN Synonyms=C6orf71, DEHAL1 {ECO:0000303|PubMed:15289438};
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] (ISOFORMS 1; 4 AND 5).
RC TISSUE=Thyroid;
RA Moreno J.C., Keijser R., Aarraas S., De Vijlder J.J.M., Ris-Stalpers C.;
RT "Cloning and characterization of a novel thyroidal gene encoding proteins
RT with a conserved nitroreductase domain.";
RL J. Endocrinol. Invest. 25 Suppl. 7:S23-S23(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
RC TISSUE=Thyroid;
RA Gnidehou S., Ohayon R., Kaniewski J., Morand S., Noel-Hudson M.-S.,
RA Virion A., Dupuy C.;
RT "Cloning and characterization of the human iodotyrosine dehalogenase
RT isoform 1C.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 7).
RC TISSUE=Thyroid;
RA Rodrigues-Serpa A.R., Laires R.S., Monteiro C.;
RT "New transcript variants of the human iodotyrosine dehalogenase gene.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-260.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-289 (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15289438; DOI=10.1096/fj.04-2023fje;
RA Gnidehou S., Caillou B., Talbot M., Ohayon R., Kaniewski J.,
RA Noel-Hudson M.-S., Morand S., Agnangji D., Sezan A., Courtin F., Virion A.,
RA Dupuy C.;
RT "Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved
RT in the recycling of iodide close to the thyroglobulin iodination site.";
RL FASEB J. 18:1574-1576(2004).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=28157283; DOI=10.1021/acs.biochem.6b01308;
RA Ingavat N., Kavran J.M., Sun Z., Rokita S.E.;
RT "Active Site Binding Is Not Sufficient for Reductive Deiodination by
RT Iodotyrosine Deiodinase.";
RL Biochemistry 56:1130-1139(2017).
RN [10] {ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC}
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 32-289 IN COMPLEX WITH
RP 3-IODO-L-TYROSINE AND FMN, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND
RP SUBUNIT.
RX PubMed=25395621; DOI=10.1074/jbc.m114.605964;
RA Hu J., Chuenchor W., Rokita S.E.;
RT "A switch between one- and two-electron chemistry of the human flavoprotein
RT iodotyrosine deiodinase is controlled by substrate.";
RL J. Biol. Chem. 290:590-600(2015).
RN [11]
RP VARIANTS TDH4 TRP-101; 105-PHE-ISO-106 DELINS LEU AND THR-116,
RP CHARACTERIZATION OF VARIANTS TDH4 TRP-101; 105-PHE-ISO-106 DELINS LEU AND
RP THR-116, MUTAGENESIS OF ARG-101; PHE-105 AND ILE-116, CATALYTIC ACTIVITY,
RP AND FUNCTION.
RX PubMed=18434651; DOI=10.1056/nejmoa0706819;
RA Moreno J.C., Klootwijk W., van Toor H., Pinto G., D'Alessandro M.,
RA Leger A., Goudie D., Polak M., Grueters A., Visser T.J.;
RT "Mutations in the iodotyrosine deiodinase gene and hypothyroidism.";
RL N. Engl. J. Med. 358:1811-1818(2008).
CC -!- FUNCTION: Catalyzes the dehalogenation of halotyrosines such as 3-
CC bromo-L-tyrosine, 3-chloro-L-tyrosine, 3-iodo-L-tyrosine and 3,5-
CC diiodo-L-tyrosine (PubMed:15289438, PubMed:18434651, PubMed:25395621,
CC PubMed:28157283). During thyroid hormone biosynthesis, facilitates
CC iodide salvage by catalysing the oxidative NADPH-dependent deiodination
CC of the halogenated by-products of thyroid hormone production,
CC monoiodotyrosine (L-MIT) and diiodotyrosine (L-DIT) (PubMed:15289438,
CC PubMed:18434651). The scavanged iodide can then reenter the hormone-
CC producing pathways (PubMed:15289438, PubMed:18434651). Acts more
CC efficiently on 3-iodo-L-tyrosine than 3,5-diiodo-L-tyrosine
CC (PubMed:15289438). {ECO:0000269|PubMed:15289438,
CC ECO:0000269|PubMed:18434651, ECO:0000269|PubMed:25395621,
CC ECO:0000269|PubMed:28157283}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 iodide + L-tyrosine + 2 NADP(+) = 3,5-diiodo-L-tyrosine +
CC H(+) + 2 NADPH; Xref=Rhea:RHEA:32479, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349; EC=1.21.1.1;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32481;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=iodide + L-tyrosine + NADP(+) = 3-iodo-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:27453, ChEBI:CHEBI:16382, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27455;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-iodo-L-tyrosine + iodide + NADP(+) = 3,5-diiodo-L-tyrosine +
CC H(+) + NADPH; Xref=Rhea:RHEA:27457, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16382, ChEBI:CHEBI:57506, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:59898;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27459;
CC Evidence={ECO:0000269|PubMed:15289438, ECO:0000269|PubMed:18434651,
CC ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride + L-tyrosine + NADP(+) = 3-chloro-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:70343, ChEBI:CHEBI:17996, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189422;
CC Evidence={ECO:0000269|PubMed:25395621};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70345;
CC Evidence={ECO:0000269|PubMed:25395621};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bromide + L-tyrosine + NADP(+) = 3-bromo-L-tyrosine + NADPH;
CC Xref=Rhea:RHEA:70347, ChEBI:CHEBI:15858, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58315, ChEBI:CHEBI:58349, ChEBI:CHEBI:189423;
CC Evidence={ECO:0000269|PubMed:25395621};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70349;
CC Evidence={ECO:0000269|PubMed:25395621};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:25395621, ECO:0000269|PubMed:28157283};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.67 uM for L-DIT {ECO:0000269|PubMed:15289438};
CC KM=1.35 uM for L-MIT {ECO:0000269|PubMed:15289438};
CC KM=7.3 uM for 3-iodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:28157283};
CC KM=4.1 mM for 2-iodophenol (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:28157283};
CC Note=kcat is 0.102 sec(-1) for the dehalogenation of 3-iodo-L-
CC tyrosine (at pH 7.4 and 25 degrees Celsius) (PubMed:28157283). kcat
CC is 0.004 sec(-1) for the dehalogenation of 2-iodophenol (at pH 7.4
CC and 25 degrees Celsius) (PubMed:28157283).
CC {ECO:0000269|PubMed:28157283};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25395621}.
CC -!- INTERACTION:
CC Q6PHW0; Q86WT6: TRIM69; NbExp=3; IntAct=EBI-10253668, EBI-749955;
CC Q6PHW0; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-10253668, EBI-11525489;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15289438};
CC Single-pass membrane protein {ECO:0000269|PubMed:15289438}. Cytoplasmic
CC vesicle membrane {ECO:0000269|PubMed:15289438}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=Q6PHW0-1; Sequence=Displayed;
CC Name=3; Synonyms=E;
CC IsoId=Q6PHW0-3; Sequence=VSP_017809, VSP_017810;
CC Name=4; Synonyms=B;
CC IsoId=Q6PHW0-4; Sequence=VSP_017805;
CC Name=5; Synonyms=C;
CC IsoId=Q6PHW0-5; Sequence=VSP_017806, VSP_017813;
CC Name=6; Synonyms=D;
CC IsoId=Q6PHW0-6; Sequence=VSP_017807, VSP_017812;
CC Name=7; Synonyms=F;
CC IsoId=Q6PHW0-7; Sequence=VSP_017802, VSP_017803, VSP_017809,
CC VSP_017810;
CC -!- TISSUE SPECIFICITY: Expressed at a high level in thyroid gland (at
CC protein level). Expressed at a high level in thyroid gland and at lower
CC level in kidney and trachea. {ECO:0000269|PubMed:15289438}.
CC -!- DISEASE: Thyroid dyshormonogenesis 4 (TDH4) [MIM:274800]: A disorder
CC due to thyroid dyshormonogenesis, causing severe hypothyroidism,
CC goiter, excessive levels of iodotyrosine in serum and urine, and
CC variable mental deficits derived from unrecognized and untreated
CC hypothyroidism. {ECO:0000269|PubMed:18434651}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY41467.1; Type=Erroneous translation; Evidence={ECO:0000305};
CC Sequence=BAC85255.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY259176; AAP22072.1; -; mRNA.
DR EMBL; AY259177; AAP22073.1; -; mRNA.
DR EMBL; AY424901; AAR84259.1; -; mRNA.
DR EMBL; AY424902; AAR84260.1; -; mRNA.
DR EMBL; AY957659; AAY41465.1; -; mRNA.
DR EMBL; AY957660; AAY41466.1; -; mRNA.
DR EMBL; AY957661; AAY41467.1; ALT_SEQ; mRNA.
DR EMBL; AL031010; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056253; AAH56253.1; -; mRNA.
DR EMBL; AK129950; BAC85255.1; ALT_INIT; mRNA.
DR CCDS; CCDS5227.1; -. [Q6PHW0-1]
DR CCDS; CCDS55066.1; -. [Q6PHW0-3]
DR CCDS; CCDS55067.1; -. [Q6PHW0-4]
DR RefSeq; NP_001158166.1; NM_001164694.1. [Q6PHW0-4]
DR RefSeq; NP_001158167.1; NM_001164695.1. [Q6PHW0-3]
DR RefSeq; NP_001305424.1; NM_001318495.1.
DR RefSeq; NP_981932.1; NM_203395.2. [Q6PHW0-1]
DR PDB; 4TTB; X-ray; 2.45 A; A/B=32-289.
DR PDB; 4TTC; X-ray; 2.65 A; A/B/C/D/E/F=32-289.
DR PDB; 5YAK; X-ray; 2.30 A; A/B/C/D/E/F=32-289.
DR PDBsum; 4TTB; -.
DR PDBsum; 4TTC; -.
DR PDBsum; 5YAK; -.
DR AlphaFoldDB; Q6PHW0; -.
DR SMR; Q6PHW0; -.
DR BioGRID; 133150; 11.
DR IntAct; Q6PHW0; 4.
DR STRING; 9606.ENSP00000229447; -.
DR DrugBank; DB03374; 3,5-Diiodotyrosine.
DR iPTMnet; Q6PHW0; -.
DR PhosphoSitePlus; Q6PHW0; -.
DR BioMuta; IYD; -.
DR DMDM; 91207083; -.
DR jPOST; Q6PHW0; -.
DR MassIVE; Q6PHW0; -.
DR PaxDb; Q6PHW0; -.
DR PeptideAtlas; Q6PHW0; -.
DR PRIDE; Q6PHW0; -.
DR ProteomicsDB; 10043; -.
DR ProteomicsDB; 67128; -. [Q6PHW0-1]
DR ProteomicsDB; 67129; -. [Q6PHW0-3]
DR ProteomicsDB; 67130; -. [Q6PHW0-4]
DR ProteomicsDB; 67131; -. [Q6PHW0-5]
DR ProteomicsDB; 67132; -. [Q6PHW0-6]
DR ProteomicsDB; 67133; -. [Q6PHW0-7]
DR Antibodypedia; 33325; 72 antibodies from 20 providers.
DR DNASU; 389434; -.
DR Ensembl; ENST00000229447.9; ENSP00000229447.5; ENSG00000009765.15. [Q6PHW0-4]
DR Ensembl; ENST00000344419.8; ENSP00000343763.4; ENSG00000009765.15. [Q6PHW0-1]
DR Ensembl; ENST00000367335.7; ENSP00000356304.3; ENSG00000009765.15. [Q6PHW0-3]
DR Ensembl; ENST00000392256.6; ENSP00000376085.2; ENSG00000009765.15. [Q6PHW0-3]
DR GeneID; 389434; -.
DR KEGG; hsa:389434; -.
DR MANE-Select; ENST00000344419.8; ENSP00000343763.4; NM_203395.3; NP_981932.1.
DR UCSC; uc003qnu.3; human. [Q6PHW0-1]
DR CTD; 389434; -.
DR DisGeNET; 389434; -.
DR GeneCards; IYD; -.
DR HGNC; HGNC:21071; IYD.
DR HPA; ENSG00000009765; Tissue enriched (thyroid).
DR MalaCards; IYD; -.
DR MIM; 274800; phenotype.
DR MIM; 612025; gene.
DR neXtProt; NX_Q6PHW0; -.
DR OpenTargets; ENSG00000009765; -.
DR Orphanet; 95716; Familial thyroid dyshormonogenesis.
DR PharmGKB; PA162392352; -.
DR VEuPathDB; HostDB:ENSG00000009765; -.
DR eggNOG; KOG3936; Eukaryota.
DR GeneTree; ENSGT00390000004348; -.
DR HOGENOM; CLU_070764_1_1_1; -.
DR InParanoid; Q6PHW0; -.
DR OMA; WVDQDLQ; -.
DR OrthoDB; 1524590at2759; -.
DR PhylomeDB; Q6PHW0; -.
DR TreeFam; TF313415; -.
DR BRENDA; 1.21.1.1; 2681.
DR PathwayCommons; Q6PHW0; -.
DR Reactome; R-HSA-209968; Thyroxine biosynthesis.
DR SignaLink; Q6PHW0; -.
DR SIGNOR; Q6PHW0; -.
DR BioGRID-ORCS; 389434; 153 hits in 1066 CRISPR screens.
DR ChiTaRS; IYD; human.
DR GeneWiki; Iodotyrosine_deiodinase; -.
DR GenomeRNAi; 389434; -.
DR Pharos; Q6PHW0; Tbio.
DR PRO; PR:Q6PHW0; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6PHW0; protein.
DR Bgee; ENSG00000009765; Expressed in right lobe of thyroid gland and 92 other tissues.
DR ExpressionAtlas; Q6PHW0; baseline and differential.
DR Genevisible; Q6PHW0; HS.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR GO; GO:0140616; F:iodotyrosine deiodinase activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0042403; P:thyroid hormone metabolic process; IDA:UniProtKB.
DR GO; GO:0006570; P:tyrosine metabolic process; IDA:UniProtKB.
DR DisProt; DP01741; -.
DR Gene3D; 3.40.109.10; -; 1.
DR InterPro; IPR029479; Nitroreductase.
DR InterPro; IPR000415; Nitroreductase-like.
DR Pfam; PF00881; Nitroreductase; 1.
DR SUPFAM; SSF55469; SSF55469; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane;
KW Congenital hypothyroidism; Cytoplasmic vesicle; Disease variant;
KW Flavoprotein; FMN; Membrane; NADP; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..289
FT /note="Iodotyrosine deiodinase 1"
FT /id="PRO_0000230278"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 29..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..58
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 100..104
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT BINDING 128..129
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9DCX8"
FT BINDING 128
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTC"
FT BINDING 130
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0007744|PDB:4TTC"
FT BINDING 157
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTC"
FT BINDING 161
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTC"
FT BINDING 182
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTC"
FT BINDING 237..239
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT BINDING 279
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:25395621,
FT ECO:0007744|PDB:4TTB, ECO:0007744|PDB:4TTC"
FT VAR_SEQ 1..55
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017802"
FT VAR_SEQ 56..61
FT /note="QAEEDA -> MKEADV (in isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017803"
FT VAR_SEQ 230..289
FT /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSKEATVPDLKRKP
FT LDQIMVTV -> VNNGITMRHQTARHRHLIEGPGRSSEACSKLSSQGCPECRSGDCHYH
FT SSQLWPSTEGAPGPPRT (in isoform 4)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_017805"
FT VAR_SEQ 230..284
FT /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSKEATVPDLKRKP
FT LDQ -> VNNGITMRHQTARHRHLIEGPGRSSEACSKLSSQGRPGASAAGSLFHFAIEF
FT AAP (in isoform 5)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_017806"
FT VAR_SEQ 230..270
FT /note="NAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYPSK -> VNNGITM
FT RHQTARHRHLIEGPGRSSEACSKLSSQGRPGFYC (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_017807"
FT VAR_SEQ 230..248
FT /note="NAGLVTVTTTPLNCGPRLR -> VFGKIILKELALISFLNL (in
FT isoform 3 and isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017809"
FT VAR_SEQ 249..289
FT /note="Missing (in isoform 3 and isoform 7)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_017810"
FT VAR_SEQ 271..289
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_017812"
FT VAR_SEQ 285..289
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_017813"
FT VARIANT 101
FT /note="R -> W (in TDH4; strongly reduces activity; does not
FT respond to the increase of flavin mononucleotide
FT concentration; dbSNP:rs121918138)"
FT /evidence="ECO:0000269|PubMed:18434651"
FT /id="VAR_045963"
FT VARIANT 105..106
FT /note="FI -> L (in TDH4; strongly reduces activity; does
FT not respond to the increase of flavin mononucleotide
FT concentration)"
FT /id="VAR_045964"
FT VARIANT 116
FT /note="I -> T (in TDH4; strongly reduces activity;
FT marginally respond to the increase of flavin mononucleotide
FT concentration; reduces protein stability;
FT dbSNP:rs121918139)"
FT /evidence="ECO:0000269|PubMed:18434651"
FT /id="VAR_045965"
FT VARIANT 260
FT /note="L -> P (in dbSNP:rs17854906)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_025785"
FT VARIANT 271
FT /note="E -> K (in dbSNP:rs36063028)"
FT /id="VAR_045966"
FT MUTAGEN 101
FT /note="R->A: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:18434651"
FT MUTAGEN 101
FT /note="R->H: Reduces activity."
FT /evidence="ECO:0000269|PubMed:18434651"
FT MUTAGEN 105
FT /note="F->A: Activity as the wild type."
FT /evidence="ECO:0000269|PubMed:18434651"
FT MUTAGEN 105
FT /note="F->Y: Activity as the wild type."
FT /evidence="ECO:0000269|PubMed:18434651"
FT MUTAGEN 116
FT /note="I->V: Activity as the wild type."
FT /evidence="ECO:0000269|PubMed:18434651"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:4TTC"
FT HELIX 83..98
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 113..123
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 135..140
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 143..162
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 167..173
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 184..187
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 189..201
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:4TTC"
FT HELIX 213..230
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 244..250
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 257..266
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:5YAK"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:5YAK"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:4TTB"
FT CONFLICT Q6PHW0-4:265
FT /note="C -> R (in Ref. 1; AAP22073)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 289 AA; 33360 MW; B73560A682BF6045 CRC64;
MYFLTPILVA ILCILVVWIF KNADRSMEKK KGEPRTRAEA RPWVDEDLKD SSDLHQAEED
ADEWQESEEN VEHIPFSHNH YPEKEMVKRS QEFYELLNKR RSVRFISNEQ VPMEVIDNVI
RTAGTAPSGA HTEPWTFVVV KDPDVKHKIR KIIEEEEEIN YMKRMGHRWV TDLKKLRTNW
IKEYLDTAPI LILIFKQVHG FAANGKKKVH YYNEISVSIA CGILLAALQN AGLVTVTTTP
LNCGPRLRVL LGRPAHEKLL MLLPVGYPSK EATVPDLKRK PLDQIMVTV
