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Q6PHW0 (IYD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Iodotyrosine dehalogenase 1

Short name=IYD-1
EC=1.22.1.1
Gene names
Name:IYD
Synonyms:C6orf71, DEHAL1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the oxidative NADPH-dependent deiodination of monoiodotyrosine (L-MIT) or diiodotyrosine (L-DIT). Acts during the hydrolysis of thyroglobulin to liberate iodide, which can then reenter the hormone-producing pathways. Acts more efficiently on monoiodotyrosine than on diiodotyrosine. Ref.7

Catalytic activity

L-tyrosine + 2 NADP+ + 2 I- = 3,5-diiodo-L-tyrosine + 2 NADPH.

Cofactor

FMN Probable.

Subunit structure

Homodimer By similarity.

Subcellular location

Cell membrane; Single-pass membrane protein Ref.7.

Tissue specificity

Expressed at a high level in thyroid gland and at lower level in kidney and trachea. Ref.7

Involvement in disease

Thyroid dyshormonogenesis 4 (TDH4) [MIM:274800]: A disorder due to thyroid dyshormonogenesis, causing severe hypothyroidism, goiter, excessive levels of iodotyrosine in serum and urine, and variable mental deficits derived from unrecognized and untreated hypothyroidism.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the nitroreductase family.

Biophysicochemical properties

Kinetic parameters:

KM=2.67 µM for L-DIT Ref.7

KM=1.35 µM for L-MIT

Sequence caution

The sequence AAY41467.1 differs from that shown. Reason: Erroneous translation.

The sequence BAC85255.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6PHW0-1)

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 3 (identifier: Q6PHW0-3)

Also known as: E;

The sequence of this isoform differs from the canonical sequence as follows:
     230-248: NAGLVTVTTTPLNCGPRLR → VFGKIILKELALISFLNL
     249-289: Missing.
Isoform 4 (identifier: Q6PHW0-4)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     230-289: NAGLVTVTTT...KPLDQIMVTV → VNNGITMRHQ...TEGAPGPPRT
Isoform 5 (identifier: Q6PHW0-5)

Also known as: C;

The sequence of this isoform differs from the canonical sequence as follows:
     230-284: NAGLVTVTTT...PDLKRKPLDQ → VNNGITMRHQ...FHFAIEFAAP
     285-289: Missing.
Isoform 6 (identifier: Q6PHW0-6)

Also known as: D;

The sequence of this isoform differs from the canonical sequence as follows:
     230-270: NAGLVTVTTT...MLLPVGYPSK → VNNGITMRHQ...SSQGRPGFYC
     271-289: Missing.
Isoform 7 (identifier: Q6PHW0-7)

Also known as: F;

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.
     56-61: QAEEDA → MKEADV
     230-248: NAGLVTVTTTPLNCGPRLR → VFGKIILKELALISFLNL
     249-289: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Potential
Chain24 – 289266Iodotyrosine dehalogenase 1
PRO_0000230278

Regions

Topological domain24 – 214191Extracellular Potential
Transmembrane215 – 23521Helical; Potential
Topological domain236 – 28954Cytoplasmic Potential
Nucleotide binding100 – 1045FMN By similarity
Nucleotide binding127 – 1293FMN By similarity
Nucleotide binding236 – 2394FMN By similarity

Sites

Binding site1041Substrate By similarity
Binding site1611Substrate By similarity
Binding site1821Substrate By similarity
Binding site2791FMN By similarity

Natural variations

Alternative sequence1 – 5555Missing in isoform 7.
VSP_017802
Alternative sequence56 – 616QAEEDA → MKEADV in isoform 7.
VSP_017803
Alternative sequence230 – 28960NAGLV…IMVTV → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGCPECR SGDCHYHSSQLWPSTEGAPG PPRT in isoform 4.
VSP_017805
Alternative sequence230 – 28455NAGLV…KPLDQ → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGRPGAS AAGSLFHFAIEFAAP in isoform 5.
VSP_017806
Alternative sequence230 – 27041NAGLV…GYPSK → VNNGITMRHQTARHRHLIEG PGRSSEACSKLSSQGRPGFY C in isoform 6.
VSP_017807
Alternative sequence230 – 24819NAGLV…GPRLR → VFGKIILKELALISFLNL in isoform 3 and isoform 7.
VSP_017809
Alternative sequence249 – 28941Missing in isoform 3 and isoform 7.
VSP_017810
Alternative sequence271 – 28919Missing in isoform 6.
VSP_017812
Alternative sequence285 – 2895Missing in isoform 5.
VSP_017813
Natural variant1011R → W in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration. Ref.8
VAR_045963
Natural variant105 – 1062FI → L in TDH4; strongly reduces activity; does not respond to the increase of flavin mononucleotide concentration.
VAR_045964
Natural variant1161I → T in TDH4; strongly reduces activity; marginally respond to the increase of flavin mononucleotide concentration; reduces protein stability. Ref.8
VAR_045965
Natural variant2601L → P. Ref.5
Corresponds to variant rs17854906 [ dbSNP | Ensembl ].
VAR_025785
Natural variant2711E → K.
Corresponds to variant rs36063028 [ dbSNP | Ensembl ].
VAR_045966

Experimental info

Mutagenesis1011R → A: Strongly reduces activity. Ref.8
Mutagenesis1011R → H: Reduces activity. Ref.8
Mutagenesis1051F → A: Activity as the wild type. Ref.8
Mutagenesis1051F → Y: Activity as the wild type. Ref.8
Mutagenesis1161I → V: Activity as the wild type. Ref.8
Isoform 4:
Sequence conflict2651C → R in AAP22073. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 4, 2006. Version 2.
Checksum: B73560A682BF6045

FASTA28933,360
        10         20         30         40         50         60 
MYFLTPILVA ILCILVVWIF KNADRSMEKK KGEPRTRAEA RPWVDEDLKD SSDLHQAEED 

        70         80         90        100        110        120 
ADEWQESEEN VEHIPFSHNH YPEKEMVKRS QEFYELLNKR RSVRFISNEQ VPMEVIDNVI 

       130        140        150        160        170        180 
RTAGTAPSGA HTEPWTFVVV KDPDVKHKIR KIIEEEEEIN YMKRMGHRWV TDLKKLRTNW 

       190        200        210        220        230        240 
IKEYLDTAPI LILIFKQVHG FAANGKKKVH YYNEISVSIA CGILLAALQN AGLVTVTTTP 

       250        260        270        280 
LNCGPRLRVL LGRPAHEKLL MLLPVGYPSK EATVPDLKRK PLDQIMVTV 

« Hide

Isoform 3 (E) [UniParc].

Checksum: 256CCEE175E985A1
Show »

FASTA24728,858
Isoform 4 (B) [UniParc].

Checksum: 2DEF1D502CC9F28E
Show »

FASTA29333,781
Isoform 5 (C) [UniParc].

Checksum: 2C8639AEB123CF4F
Show »

FASTA28432,642
Isoform 6 (D) [UniParc].

Checksum: 501B6AC58642354A
Show »

FASTA27031,367
Isoform 7 (F) [UniParc].

Checksum: 5EFAEB7D3AF9FFBC
Show »

FASTA19222,460

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel thyroidal gene encoding proteins with a conserved nitroreductase domain."
Moreno J.C., Keijser R., Aarraas S., De Vijlder J.J.M., Ris-Stalpers C.
J. Endocrinol. Invest. 25 Suppl. 7:S23-S23(2002)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 4 AND 5).
Tissue: Thyroid.
[2]"Cloning and characterization of the human iodotyrosine dehalogenase isoform 1C."
Gnidehou S., Ohayon R., Kaniewski J., Morand S., Noel-Hudson M.-S., Virion A., Dupuy C.
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
Tissue: Thyroid.
[3]"New transcript variants of the human iodotyrosine dehalogenase gene."
Rodrigues-Serpa A.R., Laires R.S., Monteiro C.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 7).
Tissue: Thyroid.
[4]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"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] (ISOFORM 1), VARIANT PRO-260.
Tissue: Kidney.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-289 (ISOFORM 1).
Tissue: Kidney.
[7]"Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site."
Gnidehou S., Caillou B., Talbot M., Ohayon R., Kaniewski J., Noel-Hudson M.-S., Morand S., Agnangji D., Sezan A., Courtin F., Virion A., Dupuy C.
FASEB J. 18:1574-1576(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[8]"Mutations in the iodotyrosine deiodinase gene and hypothyroidism."
Moreno J.C., Klootwijk W., van Toor H., Pinto G., D'Alessandro M., Leger A., Goudie D., Polak M., Grueters A., Visser T.J.
N. Engl. J. Med. 358:1811-1818(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TDH4 TRP-101; 105-PHE-ISO-106 DELINS LEU AND THR-116, CHARACTERIZATION OF VARIANTS TDH4 TRP-101; 105-PHE-ISO-106 DELINS LEU AND THR-116, MUTAGENESIS OF ARG-101; PHE-105 AND ILE-116.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY259176 mRNA. Translation: AAP22072.1.
AY259177 mRNA. Translation: AAP22073.1.
AY424901 mRNA. Translation: AAR84259.1.
AY424902 mRNA. Translation: AAR84260.1.
AY957659 mRNA. Translation: AAY41465.1.
AY957660 mRNA. Translation: AAY41466.1.
AY957661 mRNA. Translation: AAY41467.1. Sequence problems.
AL031010 Genomic DNA. No translation available.
BC056253 mRNA. Translation: AAH56253.1.
AK129950 mRNA. Translation: BAC85255.1. Different initiation.
CCDSCCDS5227.1. [Q6PHW0-1]
CCDS55066.1. [Q6PHW0-3]
CCDS55067.1. [Q6PHW0-4]
RefSeqNP_001158166.1. NM_001164694.1. [Q6PHW0-4]
NP_001158167.1. NM_001164695.1. [Q6PHW0-3]
NP_981932.1. NM_203395.2. [Q6PHW0-1]
UniGeneHs.310225.

3D structure databases

ProteinModelPortalQ6PHW0.
SMRQ6PHW0. Positions 70-289.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteQ6PHW0.

Polymorphism databases

DMDM91207083.

Proteomic databases

PaxDbQ6PHW0.
PRIDEQ6PHW0.

Protocols and materials databases

DNASU389434.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000229447; ENSP00000229447; ENSG00000009765. [Q6PHW0-4]
ENST00000344419; ENSP00000343763; ENSG00000009765. [Q6PHW0-1]
ENST00000367335; ENSP00000356304; ENSG00000009765. [Q6PHW0-3]
ENST00000392256; ENSP00000376085; ENSG00000009765. [Q6PHW0-3]
GeneID389434.
KEGGhsa:389434.
UCSCuc003qnu.2. human. [Q6PHW0-1]
uc003qnv.2. human. [Q6PHW0-3]

Organism-specific databases

CTD389434.
GeneCardsGC06P150731.
H-InvDBHIX0025059.
HGNCHGNC:21071. IYD.
HPAHPA059627.
MIM274800. phenotype.
612025. gene.
neXtProtNX_Q6PHW0.
Orphanet95716. Familial thyroid dyshormonogenesis.
PharmGKBPA162392352.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0778.
HOVERGENHBG055004.
KOK17231.
OMAQTARHRH.
OrthoDBEOG7HMS24.
PhylomeDBQ6PHW0.
TreeFamTF313415.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

BgeeQ6PHW0.
GenevestigatorQ6PHW0.

Family and domain databases

Gene3D3.40.109.10. 1 hit.
InterProIPR029479. Nitroreductase.
IPR000415. Nitroreductase-like.
[Graphical view]
PfamPF00881. Nitroreductase. 1 hit.
[Graphical view]
SUPFAMSSF55469. SSF55469. 1 hit.
ProtoNetSearch...

Other

GeneWikiIodotyrosine_deiodinase.
GenomeRNAi389434.
NextBio102878.
PROQ6PHW0.
SOURCESearch...

Entry information

Entry nameIYD1_HUMAN
AccessionPrimary (citable) accession number: Q6PHW0
Secondary accession number(s): C9JFW2 expand/collapse secondary AC list , Q2VPW0, Q2VPW1, Q5F1L5, Q5F1L6, Q5THM4, Q6ZP69, Q7Z7D7, Q7Z7D8
Entry history
Integrated into UniProtKB/Swiss-Prot: April 4, 2006
Last sequence update: April 4, 2006
Last modified: July 9, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 6

Human chromosome 6: entries, gene names and cross-references to MIM