IYD1_MOUSE
ID IYD1_MOUSE Reviewed; 285 AA.
AC Q9DCX8;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Iodotyrosine deiodinase 1 {ECO:0000303|PubMed:19777994};
DE Short=IYD-1 {ECO:0000303|PubMed:19777994};
DE EC=1.21.1.1 {ECO:0000269|PubMed:19777994, ECO:0000269|PubMed:22238141};
DE AltName: Full=Iodotyrosine dehalogenase 1 {ECO:0000250|UniProtKB:Q6PHW0};
GN Name=Iyd; Synonyms=Dehal1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; 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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, Lung, and Pancreas;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=19777994; DOI=10.1021/ja906642n;
RA McTamney P.M., Rokita S.E.;
RT "A mammalian reductive deiodinase has broad power to dehalogenate
RT chlorinated and brominated substrates.";
RL J. Am. Chem. Soc. 131:14212-14213(2009).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 34-285 IN COMPLEXES WITH
RP 3,5-DIIODOTYROSINE; 3-IODO-TYROSINE AND FMN, SUBUNIT, AND COFACTOR.
RX PubMed=19436071; DOI=10.1074/jbc.m109.013458;
RA Thomas S.R., McTamney P.M., Adler J.M., Laronde-Leblanc N., Rokita S.E.;
RT "Crystal structure of iodotyrosine deiodinase, a novel flavoprotein
RT responsible for iodide salvage in thyroid glands.";
RL J. Biol. Chem. 284:19659-19667(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 34-285 IN COMPLEX WITH
RP 3-IODO-L-TYROSINE AND FMN, FUNCTION, COFACTOR, CATALYTIC ACTIVITY, SUBUNIT,
RP AND MUTAGENESIS OF GLU-153.
RX PubMed=22238141; DOI=10.1002/pro.2020;
RA Buss J.M., McTamney P.M., Rokita S.E.;
RT "Expression of a soluble form of iodotyrosine deiodinase for active site
RT characterization by engineering the native membrane protein from Mus
RT musculus.";
RL Protein Sci. 21:351-361(2012).
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 (By similarity). During thyroid hormone biosynthesis,
CC facilitates iodide salvage by catalysing the oxidative NADPH-dependent
CC deiodination of the halogenated by-products of thyroid hormone
CC production, monoiodotyrosine (L-MIT) and diiodotyrosine (L-DIT)
CC (PubMed:22238141). The scavanged iodide can then reenter the hormone-
CC producing pathways (By similarity). Acts more efficiently on 3-iodo-L-
CC tyrosine than 3,5-diiodo-L-tyrosine (By similarity).
CC {ECO:0000250|UniProtKB:Q6PHW0, ECO:0000269|PubMed:22238141}.
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:22238141};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32481;
CC Evidence={ECO:0000269|PubMed:22238141};
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:22238141};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27455;
CC Evidence={ECO:0000269|PubMed:22238141};
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:22238141};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27459;
CC Evidence={ECO:0000269|PubMed:22238141};
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:19777994};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70345;
CC Evidence={ECO:0000269|PubMed:19777994};
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:19777994};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70349;
CC Evidence={ECO:0000269|PubMed:19777994};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:19436071, ECO:0000269|PubMed:19777994,
CC ECO:0000269|PubMed:22238141};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19436071,
CC ECO:0000269|PubMed:22238141}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q6PHW0};
CC Single-pass membrane protein {ECO:0000250|UniProtKB:Q6PHW0}.
CC Cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q6PHW0}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
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DR EMBL; AK002363; BAB22041.1; -; mRNA.
DR EMBL; BC023358; AAH23358.1; -; mRNA.
DR CCDS; CCDS56670.1; -.
DR RefSeq; NP_081667.1; NM_027391.3.
DR PDB; 3GB5; X-ray; 2.00 A; A=34-285.
DR PDB; 3GFD; X-ray; 2.45 A; A/B=34-285.
DR PDB; 3GH8; X-ray; 2.61 A; A/B/C/D/E/F/G/H=34-285.
DR PDB; 3TNZ; X-ray; 2.25 A; A/B=34-285.
DR PDB; 3TO0; X-ray; 2.66 A; A/B=34-285.
DR PDBsum; 3GB5; -.
DR PDBsum; 3GFD; -.
DR PDBsum; 3GH8; -.
DR PDBsum; 3TNZ; -.
DR PDBsum; 3TO0; -.
DR AlphaFoldDB; Q9DCX8; -.
DR SMR; Q9DCX8; -.
DR STRING; 10090.ENSMUSP00000019896; -.
DR iPTMnet; Q9DCX8; -.
DR PhosphoSitePlus; Q9DCX8; -.
DR jPOST; Q9DCX8; -.
DR MaxQB; Q9DCX8; -.
DR PaxDb; Q9DCX8; -.
DR PeptideAtlas; Q9DCX8; -.
DR PRIDE; Q9DCX8; -.
DR ProteomicsDB; 269023; -.
DR Antibodypedia; 33325; 72 antibodies from 20 providers.
DR DNASU; 70337; -.
DR Ensembl; ENSMUST00000019896; ENSMUSP00000019896; ENSMUSG00000019762.
DR GeneID; 70337; -.
DR KEGG; mmu:70337; -.
DR UCSC; uc007ehp.1; mouse.
DR CTD; 389434; -.
DR MGI; MGI:1917587; Iyd.
DR VEuPathDB; HostDB:ENSMUSG00000019762; -.
DR eggNOG; KOG3936; Eukaryota.
DR GeneTree; ENSGT00390000004348; -.
DR HOGENOM; CLU_070764_1_0_1; -.
DR InParanoid; Q9DCX8; -.
DR OMA; WVDQDLQ; -.
DR OrthoDB; 1524590at2759; -.
DR PhylomeDB; Q9DCX8; -.
DR TreeFam; TF313415; -.
DR BRENDA; 1.21.1.1; 3474.
DR Reactome; R-MMU-209968; Thyroxine biosynthesis.
DR BioGRID-ORCS; 70337; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Iyd; mouse.
DR EvolutionaryTrace; Q9DCX8; -.
DR PRO; PR:Q9DCX8; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q9DCX8; protein.
DR Bgee; ENSMUSG00000019762; Expressed in left lobe of liver and 55 other tissues.
DR Genevisible; Q9DCX8; MM.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0006570; P:tyrosine metabolic process; IDA:UniProtKB.
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; Cell membrane; Cytoplasmic vesicle; Flavoprotein; FMN;
KW Membrane; NADP; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..285
FT /note="Iodotyrosine deiodinase 1"
FT /id="PRO_0000230279"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 96..100
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GB5,
FT ECO:0007744|PDB:3GFD, ECO:0007744|PDB:3GH8,
FT ECO:0007744|PDB:3TNZ, ECO:0007744|PDB:3TO0"
FT BINDING 124..125
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GB5,
FT ECO:0007744|PDB:3GFD, ECO:0007744|PDB:3GH8,
FT ECO:0007744|PDB:3TNZ, ECO:0007744|PDB:3TO0"
FT BINDING 126
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0007744|PDB:3GH8"
FT BINDING 126
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0007744|PDB:3GFD, ECO:0007744|PDB:3TNZ"
FT BINDING 153
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0007744|PDB:3GH8"
FT BINDING 153
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GFD,
FT ECO:0007744|PDB:3TNZ"
FT BINDING 157
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0007744|PDB:3GH8"
FT BINDING 157
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GFD,
FT ECO:0007744|PDB:3TNZ"
FT BINDING 178
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0007744|PDB:3GH8"
FT BINDING 178
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GFD,
FT ECO:0007744|PDB:3TNZ"
FT BINDING 233..235
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GB5,
FT ECO:0007744|PDB:3GFD, ECO:0007744|PDB:3GH8,
FT ECO:0007744|PDB:3TNZ, ECO:0007744|PDB:3TO0"
FT BINDING 275
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000269|PubMed:19436071,
FT ECO:0000269|PubMed:22238141, ECO:0007744|PDB:3GB5,
FT ECO:0007744|PDB:3GFD, ECO:0007744|PDB:3GH8,
FT ECO:0007744|PDB:3TNZ, ECO:0007744|PDB:3TO0"
FT MUTAGEN 153
FT /note="E->Q: Loss of enzyme activity."
FT /evidence="ECO:0000269|PubMed:22238141"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:3TNZ"
FT HELIX 79..94
FT /evidence="ECO:0007829|PDB:3GB5"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:3GB5"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:3GB5"
FT HELIX 139..151
FT /evidence="ECO:0007829|PDB:3GB5"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:3GH8"
FT HELIX 163..169
FT /evidence="ECO:0007829|PDB:3TNZ"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:3TNZ"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 184..193
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3TNZ"
FT HELIX 209..226
FT /evidence="ECO:0007829|PDB:3GB5"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:3GB5"
FT HELIX 240..246
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 253..262
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:3TNZ"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:3GB5"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:3TNZ"
SQ SEQUENCE 285 AA; 32814 MW; 7B7415D6C28B1A58 CRC64;
MFLLTPVLVA VVCILVVWVF KNADRNLEKK KEEAQVQPWV DEDLKDSTED LQVEEDAEEW
QEAEESVEHI PFSHTRYPEQ EMRMRSQEFY ELLNKRRSVR FISSEHVPME VIENVIKAAG
TAPSGAHTEP WTFVVVKDPD MKHKIREIIE EEEEINYMKR MGKRWVTDLK KLRTNWIKEY
LDTAPVLILI FKQVHGFAAN GKKKVHYYNE ISVSIACGLL LAALQNAGLV TVTTTPLNCG
PRLRVLLGRP SHEKLLVLLP VGYPSRDATV PDLKRKALDQ IMVTV
