IYD_DROME
ID IYD_DROME Reviewed; 287 AA.
AC E1JIB2;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Iodotyrosine deiodinase {ECO:0000312|FlyBase:FBgn0286980};
DE EC=1.21.1.1 {ECO:0000269|PubMed:27643701};
DE AltName: Full=Halotyrosine dehalogenase {ECO:0000305|PubMed:27643701};
DE AltName: Full=Protein condet {ECO:0000303|PubMed:27643701};
GN Name=Iyd {ECO:0000312|FlyBase:FBgn0286980};
GN Synonyms=cdt {ECO:0000303|PubMed:27643701};
GN ORFNames=CG46438 {ECO:0000312|FlyBase:FBgn0286980};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND
RP MUTAGENESIS OF GLU-154; TYR-158 AND LYS-179.
RX PubMed=27643701; DOI=10.1002/pro.3044;
RA Phatarphekar A., Rokita S.E.;
RT "Functional analysis of iodotyrosine deiodinase from drosophila
RT melanogaster.";
RL Protein Sci. 25:2187-2195(2016).
RN [4] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP GLU-154.
RX PubMed=29764939; DOI=10.1074/jbc.ra118.003364;
RA Phatarphekar A., Su Q., Eun S.H., Chen X., Rokita S.E.;
RT "The importance of a halotyrosine dehalogenase for Drosophila fertility.";
RL J. Biol. Chem. 293:10314-10321(2018).
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:27643701). Activity towards 3-fluoro-L-
CC tyrosine is weak (PubMed:27643701). Important for male and female
CC fertility (PubMed:29764939). May be involved in maintaining the
CC viability of sperm, both during development in the testes and storage
CC in the female spermatheca (PubMed:29764939).
CC {ECO:0000269|PubMed:27643701, ECO:0000269|PubMed:29764939}.
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:27643701};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:32481;
CC Evidence={ECO:0000269|PubMed:27643701};
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:27643701};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27455;
CC Evidence={ECO:0000269|PubMed:27643701};
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:27643701};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:27459;
CC Evidence={ECO:0000269|PubMed:27643701};
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:27643701};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70345;
CC Evidence={ECO:0000269|PubMed:27643701};
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:27643701};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70349;
CC Evidence={ECO:0000269|PubMed:27643701};
CC -!- COFACTOR:
CC Name=FMN; Xref=ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:27643701};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14 uM for 3-iodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:27643701};
CC KM=8 uM for 3-bromo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:27643701};
CC KM=21 uM for 3-chloro-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:27643701};
CC KM=11 uM for 3,5-diiodo-L-tyrosine (at pH 7.4 and 25 degrees Celsius)
CC {ECO:0000269|PubMed:27643701};
CC Note=kcat is 12 sec(-1) for the dehalogenation of 3-iodo-L-tyrosine
CC (at pH 7.4 and 25 degrees Celsius) (PubMed:27643701). kcat is 6.9
CC sec(-1) for the dehalogenation of 3-bromo-L-tyrosine (at pH 7.4 and
CC 25 degrees Celsius) (PubMed:27643701). kcat is 5.0 sec(-1) for the
CC dehalogenation of 3-chloro-L-tyrosine (at pH 7.4 and 25 degrees
CC Celsius) (PubMed:27643701). kcat is 10.8 sec(-1) for the
CC dehalogenation of 3,5-diiodo-L-tyrosine (at pH 7.4 and 25 degrees
CC Celsius) (PubMed:27643701). {ECO:0000269|PubMed:27643701};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q6PHW0}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in spermatocytes.
CC {ECO:0000269|PubMed:29764939}.
CC -!- DISRUPTION PHENOTYPE: Adults produce fewer progeny (PubMed:29764939).
CC Larvae display an increase in survival when fed a diet enriched with 3-
CC chloro-L-tyrosine (Cl-Tyr), whereas survival is unaffected when fed a
CC diet containing 3-iodo-L-tyrosine (I-Tyr) or 3-bromo-L-tyrosine (Br-
CC Tyr) (PubMed:29764939). Adult survival is unaffected when fed a diet
CC supplemented with halotyrosines (PubMed:29764939).
CC {ECO:0000269|PubMed:29764939}.
CC -!- MISCELLANEOUS: Named condet in honor of Dr. Jean Francois Condet who
CC discovered that ingestion of iodide could reduce goiter.
CC {ECO:0000269|PubMed:27643701}.
CC -!- SIMILARITY: Belongs to the nitroreductase family. {ECO:0000305}.
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DR EMBL; AE014296; ACZ94685.1; -; Genomic_DNA.
DR EMBL; AE014296; QJC18614.1; -; Genomic_DNA.
DR RefSeq; NP_001163414.1; NM_001169943.1.
DR SMR; E1JIB2; -.
DR PRIDE; E1JIB2; -.
DR EnsemblMetazoa; FBtr0475275; FBpp0423399; FBgn0286980.
DR EnsemblMetazoa; FBtr0475279; FBpp0423404; FBgn0286980.
DR GeneID; 39242; -.
DR KEGG; dme:Dmel_CG46438; -.
DR CTD; 389434; -.
DR FlyBase; FBgn0286980; Iyd.
DR VEuPathDB; VectorBase:FBgn0286980; -.
DR GeneTree; ENSGT00390000004348; -.
DR HOGENOM; CLU_403487_0_0_1; -.
DR OMA; WVDQDLQ; -.
DR OrthoDB; 887662at2759; -.
DR BRENDA; 1.21.1.1; 1994.
DR BioGRID-ORCS; 39242; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 39242; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Genevisible; E1JIB2; DM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010181; F:FMN binding; IDA:UniProtKB.
DR GO; GO:0004447; F:iodide peroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0140616; F:iodotyrosine deiodinase activity; IDA:FlyBase.
DR GO; GO:1905516; P:positive regulation of fertilization; IMP: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 Cell membrane; Flavoprotein; FMN; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..287
FT /note="Iodotyrosine deiodinase"
FT /id="PRO_0000455636"
FT TRANSMEM 15..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 96..100
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q6PHW0"
FT BINDING 125..126
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q9DCX8"
FT BINDING 125
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q6PHW0"
FT BINDING 127
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000250|UniProtKB:Q9DCX8"
FT BINDING 127
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000250|UniProtKB:Q9DCX8"
FT BINDING 154
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 154
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 158
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 158
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 179
FT /ligand="3,5-diiodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:57506"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 179
FT /ligand="3-iodo-L-tyrosine"
FT /ligand_id="ChEBI:CHEBI:59898"
FT /evidence="ECO:0000269|PubMed:27643701"
FT BINDING 235..237
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q6PHW0"
FT BINDING 277
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000250|UniProtKB:Q6PHW0"
FT MUTAGEN 154
FT /note="E->Q: Significant decrease in catalytic efficiency
FT and reduced affinity for substrates 3-iodo-L-tyrosine (I-
FT Tyr) and 3,5-diiodo-L-tyrosine (I2-Tyr). Larvae survival is
FT decreased when fed a diet supplemented with 100 or 200um of
FT I-Tyr but is increased when fed a diet enriched with 3-
FT chloro-L-tyrosine (Cl-Tyr). However, adult survival is
FT unaffected when fed a diet supplemented with
FT halotyrosines."
FT /evidence="ECO:0000269|PubMed:27643701,
FT ECO:0000269|PubMed:29764939"
FT MUTAGEN 158
FT /note="Y->F: Moderate decrease in catalytic efficiency and
FT reduced affinity for substrates I-Tyr and I2-Tyr."
FT /evidence="ECO:0000269|PubMed:27643701"
FT MUTAGEN 179
FT /note="K->Q: Moderate decrease in catalytic activity but
FT strongly reduces affinity for substrates I-Tyr and I2-Tyr."
FT /evidence="ECO:0000269|PubMed:27643701"
SQ SEQUENCE 287 AA; 32597 MW; D7128DE1D178EC7C CRC64;
MDVDELISSS KLLKHWPSLF ITLALIWIVK RLFFKGNRVL KTYNLDEQVE EEVEHFADLG
DELQPALEDK PHVPFVPGQN LNPNGAKRLY ELMRGRRSIR SFNSHPKPDL SVIEDCIRAA
GTAPSGAHTE PWTYCVVQEP ELKRSIREIV EQEELVNYSQ RMHPQWVTDL RPLQTNHVKE
YLTEAPYLIL IFKQTYGLSE NGKRMRRHYY NEISTSIAAG ILLCALQAAG LASLVTTPLN
CGPALRNLLG RPVNEKLLIL LPVGYPKDGC TVPDLARKNL SNIMVTF
