LOCUS       NM_001362               1958 bp    mRNA    linear   PRI 01-MAY-2025
DEFINITION  Homo sapiens iodothyronine deiodinase 3 (DIO3), mRNA.
ACCESSION   NM_001362
VERSION     NM_001362.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 1958)
  AUTHORS   Qi,Y., Meng,X., Li,J., He,A., Hao,J., Zhao,X., Zhao,R., Chen,R. and
            Zhang,R.
  TITLE     Evaluating the link between DIO3-FA27 promoter methylation,
            biochemical indices, and heart failure progression
  JOURNAL   Clin Epigenetics 16 (1), 57 (2024)
   PUBMED   38659084
  REMARK    GeneRIF: Evaluating the link between DIO3-FA27 promoter
            methylation, biochemical indices, and heart failure progression.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 1958)
  AUTHORS   Smith,C.M., Catchpoole,D. and Hutvagner,G.
  TITLE     MiRNAs from the Dlk1-Dio3 locus and miR-224/452 cluster contribute
            to glioblastoma tumor heterogeneity
  JOURNAL   Sci Rep 14 (1), 8570 (2024)
   PUBMED   38609422
  REMARK    GeneRIF: MiRNAs from the Dlk1-Dio3 locus and miR-224/452 cluster
            contribute to glioblastoma tumor heterogeneity.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1958)
  AUTHORS   Sanceau,J., Poupel,L., Joubel,C., Lagoutte,I., Caruso,S., Pinto,S.,
            Desbois-Mouthon,C., Godard,C., Hamimi,A., Montmory,E., Dulary,C.,
            Chantalat,S., Roehrig,A., Muret,K., Saint-Pierre,B., Deleuze,J.F.,
            Mouillet-Richard,S., Forne,T., Grosset,C.F., Zucman-Rossi,J.,
            Colnot,S. and Gougelet,A.
  TITLE     DLK1/DIO3 locus upregulation by a beta-catenin-dependent enhancer
            drives cell proliferation and liver tumorigenesis
  JOURNAL   Mol Ther 32 (4), 1125-1143 (2024)
   PUBMED   38311851
  REMARK    GeneRIF: DLK1/DIO3 locus upregulation by a beta-catenin-dependent
            enhancer drives cell proliferation and liver tumorigenesis.
REFERENCE   4  (bases 1 to 1958)
  AUTHORS   Liu,M., Yu,Z., Zhao,Z., Yang,F., Zhou,M., Wang,C., Tian,X.,
            Zhang,B., Liang,G., Liu,X. and Shao,J.
  TITLE     MiR-24-3p/Dio3 axis is essential for BDE47 to induce local thyroid
            hormone disorder and neurotoxicity
  JOURNAL   Toxicology 491, 153527 (2023)
   PUBMED   37116683
  REMARK    GeneRIF: MiR-24-3p/Dio3 axis is essential for BDE47 to induce local
            thyroid hormone disorder and neurotoxicity.
REFERENCE   5  (bases 1 to 1958)
  AUTHORS   Sibilio,A., Ambrosio,R., Bonelli,C., De Stefano,M.A., Torre,V.,
            Dentice,M. and Salvatore,D.
  TITLE     Deiodination in cancer growth: the role of type III deiodinase
  JOURNAL   Minerva Endocrinol 37 (4), 315-327 (2012)
   PUBMED   23235188
  REMARK    GeneRIF: D3 expression is re-activated in various types of human
            cancers. It may play a role in carcinogenesis and neoplastic cell
            proliferation. Review.
            Review article
REFERENCE   6  (bases 1 to 1958)
  AUTHORS   Hernandez,A.
  TITLE     Structure and function of the type 3 deiodinase gene
  JOURNAL   Thyroid 15 (8), 865-874 (2005)
   PUBMED   16131329
  REMARK    GeneRIF: structure and function of the type 3 deiodinase gene
            [review]
            Review article
REFERENCE   7  (bases 1 to 1958)
  AUTHORS   Baqui,M., Botero,D., Gereben,B., Curcio,C., Harney,J.W.,
            Salvatore,D., Sorimachi,K., Larsen,P.R. and Bianco,A.C.
  TITLE     Human type 3 iodothyronine selenodeiodinase is located in the
            plasma membrane and undergoes rapid internalization to endosomes
  JOURNAL   J Biol Chem 278 (2), 1206-1211 (2003)
   PUBMED   12419801
  REMARK    GeneRIF: study demonstrates that D3 is located in the plasma
            membrane with most of its molecule in the extracellular space,
            allowing access to inactivate both the hormone T3 and prohormone T4
REFERENCE   8  (bases 1 to 1958)
  AUTHORS   Hernandez,A., Park,J.P., Lyon,G.J., Mohandas,T.K. and St
            Germain,D.L.
  TITLE     Localization of the type 3 iodothyronine deiodinase (DIO3) gene to
            human chromosome 14q32 and mouse chromosome 12F1
  JOURNAL   Genomics 53 (1), 119-121 (1998)
   PUBMED   9787088
REFERENCE   9  (bases 1 to 1958)
  AUTHORS   Salvatore,D., Low,S.C., Berry,M., Maia,A.L., Harney,J.W.,
            Croteau,W., St Germain,D.L. and Larsen,P.R.
  TITLE     Type 3 lodothyronine deiodinase: cloning, in vitro expression, and
            functional analysis of the placental selenoenzyme
  JOURNAL   J Clin Invest 96 (5), 2421-2430 (1995)
   PUBMED   7593630
REFERENCE   10 (bases 1 to 1958)
  AUTHORS   Visser,T.J. and Schoenmakers,C.H.
  TITLE     Characteristics of type III iodothyronine deiodinase
  JOURNAL   Acta Med Austriaca 19 Suppl 1, 18-21 (1992)
   PUBMED   1519445
  REMARK    Review article
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL049836.3.
            
            On Apr 19, 2022 this sequence version replaced NM_001362.3.
            
            Summary: The protein encoded by this intronless gene belongs to the
            iodothyronine deiodinase family. It catalyzes the inactivation of
            thyroid hormone by inner ring deiodination of the prohormone
            thyroxine (T4) and the bioactive hormone 3,3',5-triiodothyronine
            (T3) to inactive metabolites, 3,3',5'-triiodothyronine (RT3) and
            3,3'-diiodothyronine (T2), respectively. This enzyme is highly
            expressed in pregnant uterus, placenta, fetal and neonatal tissues,
            and thought to prevent premature exposure of developing fetal
            tissues to adult levels of thyroid hormones. It regulates
            circulating fetal thyroid hormone concentrations, and thus plays a
            critical role in mammalian development. Knockout mice lacking this
            gene exhibit abnormalities related to development and reproduction,
            and increased activity of this enzyme in infants with hemangiomas
            causes severe hypothyroidism. This protein is a selenoprotein,
            containing the rare selenocysteine (Sec) amino acid at its active
            site. Sec is encoded by the UGA codon, which normally signals
            translation termination. The 3' UTRs of selenoprotein mRNAs contain
            a conserved stem-loop structure, designated the Sec insertion
            sequence (SECIS) element, that is necessary for the recognition of
            UGA as a Sec codon rather than as a stop signal. [provided by
            RefSeq, May 2016].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript is intronless :: BC017717.1, AK292310.1 [ECO:0000345]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match              :: ENST00000510508.5/
                                               ENSP00000427336.3
            protein contains selenocysteine :: PMID: 7593630
            RefSeq Select criteria          :: based on single protein-coding
                                               transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1958              AL049836.3         116018-117975
FEATURES             Location/Qualifiers
     source          1..1958
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q32.31"
     gene            1..1958
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /note="iodothyronine deiodinase 3"
                     /db_xref="GeneID:1735"
                     /db_xref="HGNC:HGNC:2885"
                     /db_xref="MIM:601038"
     exon            1..1958
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /inference="alignment:Splign:2.1.0"
     CDS             3..917
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /EC_number="1.21.99.3"
                     /note="UGA stop codon recoded as selenocysteine; type 3
                     iodothyronine selenodeiodinase; type-III 5' deiodinase;
                     iodothyronine deiodinase, placental type; thyroxine
                     deiodinase type III (selenoprotein); type 3 DI;
                     deiodinase, iodothyronine type III; selenoprotein DIO3"
                     /codon_start=1
                     /transl_except=(pos:510..512,aa:Sec)
                     /product="thyroxine 5-deiodinase"
                     /protein_id="NP_001353.4"
                     /db_xref="CCDS:CCDS41992.2"
                     /db_xref="GeneID:1735"
                     /db_xref="HGNC:HGNC:2885"
                     /db_xref="MIM:601038"
                     /translation="MPRQATSRLVVGEGEGSQGASGPAATMLRSLLLHSLRLCAQTAS
                     CLVLFPRFLGTAFMLWLLDFLCIRKHFLGRRRRGQPEPEVELNSEGEEVPPDDPPICV
                     SDDNRLCTLASLKAVWHGQKLDFFKQAHEGGPAPNSEVVLPDGFQSQHILDYAQGNRP
                     LVLNFGSCTUPPFMARMSAFQRLVTKYQRDVDFLIIYIEEAHPSDGWVTTDSPYIIPQ
                     HRSLEDRVSAARVLQQGAPGCALVLDTMANSSSSAYGAYFERLYVIQSGTIMYQGGRG
                     PDGYQVSELRTWLERYDEQLHGARPRRV"
     regulatory      1498..1571
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      1934..1939
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /note="hexamer: AATAAA"
     polyA_site      1956
                     /gene="DIO3"
                     /gene_synonym="5DIII; D3; DIOIII; TXDI3"
                     /note="major polyA site"
ORIGIN      
        1 agatgcctcg ccaggccacg tcgcggttgg tggtcggaga gggcgagggg tcccaggggg
       61 cttcggggcc tgcagccacc atgctccgct ccctgctgct tcactccttg aggctctgcg
      121 cccagaccgc ctcgtgcctc gtgctcttcc cgcgcttcct cggcacggcc ttcatgctct
      181 ggcttctcga tttcttgtgt atccgcaagc atttcctggg ccgccgccgc cgggggcagc
      241 ccgagcccga agtggagctc aacagtgaag gcgaggaggt gcctcccgat gacccgccca
      301 tctgcgtgtc cgacgacaac cgcctgtgca ccctggcgtc gctcaaggcg gtgtggcatg
      361 gccagaagtt ggatttcttc aagcaggcgc acgagggcgg tccggcgccc aactccgagg
      421 tggttctgcc cgacggcttc cagagccagc acatcctcga ctacgcgcaa gggaaccgcc
      481 cgctggttct caatttcggc agctgcacct gaccaccgtt catggcgcgc atgagcgcct
      541 tccagcgcct ggtcactaag taccagcgcg acgtcgactt cctcatcatc tacatcgagg
      601 aagcgcaccc ctccgacggc tgggtcacca cggactctcc ctacatcatc ccacagcacc
      661 ggagcctgga ggaccgggtc agcgcagcga gggtactgca gcaaggtgca cccggctgcg
      721 ctctggtcct cgacaccatg gccaactcca gcagctcggc ctatggcgcc tacttcgagc
      781 gtctctatgt catccagagt ggcactatta tgtaccaggg cggccgtggc cccgacggct
      841 accaggtctc tgagctgcgc acttggttgg aacgctatga tgagcaactg cacggcgctc
      901 ggccccggag ggtgtaaaca tccaacggac aattgactga acttggtggg ctgggccttc
      961 gagccttcga agcccacgtg caagcgcctc aaaccaagtc acgcttggcg aggccccagt
     1021 gacactgatg tgctgagcca ccatttcaga ctgagtctgc accctcagcc acatgaacaa
     1081 tctcccctac ctccctggga ctctgcttct gtaactgtct cattcacacc tgcctggctc
     1141 actggaaatc ctcttttgag cgcgggatat ggcttgccct tgtccgtgtg cccccaggac
     1201 tttgcctcta cagcattttc ttacaccccc tccccagcgt gccctcagcc aagtgctttg
     1261 gcccggtgct tcccgcagct gcacagagac cttggccacg cccgcgcgcc ctgagcgcag
     1321 ctgggttcca ggagactctc agctcagctg agctagttgc ctggcaccca cctgtcgcgc
     1381 gcggagaggg ggttccctgt tgcttttgtg tctgtttcct gtccctggta ggggaagtga
     1441 tgtcgtggat ggggaggggt gggcagggta gtttcccccg cttgttttgg gtgcacagga
     1501 gccccactgc tgatgacgaa ctatctctaa ctggtcttga ccacgagcta gttctgaatt
     1561 gcaggggcct caaagcagca cctaaacctt gagggggagg gtgctctggg tttccgtgag
     1621 gtaaccacct taaatgggag ggaagttggg gtgtctgctt tgggaccaga ggaagatagc
     1681 ttgagaggca ttggcgaggt tcgcagcgcc ccagggagag agaaaaagct gagactcctg
     1741 gggaatgacg ttggggtgat ggagtccggg gaaagagagg tggggggaga gcctgaggtc
     1801 cccaagtgag gggagtccta ggcagagctg ctgattgtgg ggctgggagg tggagggccc
     1861 ctgattcgaa ggccatttgg tgagtgtttt gctggaaata tttcctgtat ataaacttct
     1921 ttcaatctac aataataaag gcttgaggta aactgctt
//
