LOCUS       NM_013989               6017 bp    mRNA    linear   PRI 15-JUL-2024
DEFINITION  Homo sapiens iodothyronine deiodinase 2 (DIO2), transcript variant
            1, mRNA.
ACCESSION   NM_013989
VERSION     NM_013989.5
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 6017)
  AUTHORS   Beltrao,D.C.A., Beltrao,F.E.L., Carvalhal,G., Beltrao,F.L.L.,
            Brito,A.D.S., Silva,H.D.S., Teixeira,H.M.P., Rodrigues,J.L., de
            Figueiredo,C.A.V., Costa,R.D.S., Pordeus,L.C.M., Vieira,G.C. and
            Ramos,H.E.
  TITLE     The Thr92Ala polymorphism in the type 2 deiodinase gene is linked
            to depression in patients with COVID-19 after hospital discharge
  JOURNAL   Front Endocrinol (Lausanne) 15, 1366500 (2024)
   PUBMED   38911040
  REMARK    GeneRIF: The Thr92Ala polymorphism in the type 2 deiodinase gene is
            linked to depression in patients with COVID-19 after hospital
            discharge.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 6017)
  AUTHORS   Ohba,K., Yoshioka,T. and Muraki,T.
  TITLE     Identification of two novel splicing variants of human type II
            iodothyronine deiodinase mRNA
  JOURNAL   Mol Cell Endocrinol 172 (1-2), 169-175 (2001)
   PUBMED   11165050
REFERENCE   3  (bases 1 to 6017)
  AUTHORS   Baqui,M.M., Gereben,B., Harney,J.W., Larsen,P.R. and Bianco,A.C.
  TITLE     Distinct subcellular localization of transiently expressed types 1
            and 2 iodothyronine deiodinases as determined by immunofluorescence
            confocal microscopy
  JOURNAL   Endocrinology 141 (11), 4309-4312 (2000)
   PUBMED   11089566
REFERENCE   4  (bases 1 to 6017)
  AUTHORS   Bartha,T., Kim,S.W., Salvatore,D., Gereben,B., Tu,H.M.,
            Harney,J.W., Rudas,P. and Larsen,P.R.
  TITLE     Characterization of the 5'-flanking and 5'-untranslated regions of
            the cyclic adenosine 3',5'-monophosphate-responsive human type 2
            iodothyronine deiodinase gene
  JOURNAL   Endocrinology 141 (1), 229-237 (2000)
   PUBMED   10614643
REFERENCE   5  (bases 1 to 6017)
  AUTHORS   Salvatore,D., Harney,J.W. and Larsen,P.R.
  TITLE     Mutation of the Secys residue 266 in human type 2 selenodeiodinase
            alters 75Se incorporation without affecting its biochemical
            properties
  JOURNAL   Biochimie 81 (5), 535-538 (1999)
   PUBMED   10403186
REFERENCE   6  (bases 1 to 6017)
  AUTHORS   Buettner,C., Harney,J.W. and Larsen,P.R.
  TITLE     The 3'-untranslated region of human type 2 iodothyronine deiodinase
            mRNA contains a functional selenocysteine insertion sequence
            element
  JOURNAL   J Biol Chem 273 (50), 33374-33378 (1998)
   PUBMED   9837913
REFERENCE   7  (bases 1 to 6017)
  AUTHORS   Celi,F.S., Canettieri,G., Yarnall,D.P., Burns,D.K., Andreoli,M.,
            Shuldiner,A.R. and Centanni,M.
  TITLE     Genomic characterization of the coding region of the human type II
            5'-deiodinase gene
  JOURNAL   Mol Cell Endocrinol 141 (1-2), 49-52 (1998)
   PUBMED   9723885
REFERENCE   8  (bases 1 to 6017)
  AUTHORS   Salvatore,D., Tu,H., Harney,J.W. and Larsen,P.R.
  TITLE     Type 2 iodothyronine deiodinase is highly expressed in human
            thyroid
  JOURNAL   J Clin Invest 98 (4), 962-968 (1996)
   PUBMED   8770868
REFERENCE   9  (bases 1 to 6017)
  AUTHORS   Croteau,W., Davey,J.C., Galton,V.A. and St Germain,D.L.
  TITLE     Cloning of the mammalian type II iodothyronine deiodinase. A
            selenoprotein differentially expressed and regulated in human and
            rat brain and other tissues
  JOURNAL   J Clin Invest 98 (2), 405-417 (1996)
   PUBMED   8755651
REFERENCE   10 (bases 1 to 6017)
  AUTHORS   Mandel,S.J., Berry,M.J., Kieffer,J.D., Harney,J.W., Warne,R.L. and
            Larsen,P.R.
  TITLE     Cloning and in vitro expression of the human selenoprotein, type I
            iodothyronine deiodinase
  JOURNAL   J Clin Endocrinol Metab 75 (4), 1133-1139 (1992)
   PUBMED   1400883
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AF093774.1, BC136514.1 and
            AC007372.4.
            
            On Oct 7, 2018 this sequence version replaced NM_013989.4.
            
            Summary: The protein encoded by this gene belongs to the
            iodothyronine deiodinase family. It catalyzes the conversion of
            prohormone thyroxine (3,5,3',5'-tetraiodothyronine, T4) to the
            bioactive thyroid hormone (3,5,3'-triiodothyronine, T3) by outer
            ring 5'-deiodination. This gene is widely expressed, including in
            thyroid and brain. It is thought to be responsible for the 'local'
            production of T3, and thus important in influencing thyroid hormone
            action in these tissues. It has also been reported to be highly
            expressed in thyroids of patients with Graves disease, and in
            follicular adenomas. The intrathyroidal T4 to T3 conversion by this
            enzyme may contribute significantly to the relative increase in
            thyroidal T3 production in these patients. This protein is a
            selenoprotein containing the non-standard amino acid,
            selenocysteine (Sec), which is encoded by the UGA codon that
            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. Unlike the other two members (DIO1 and DIO3) of this
            enzyme family, the mRNA for this gene contains an additional
            in-frame UGA codon that has been reported (in human) to function
            either as a Sec or a stop codon, which can result in two isoforms
            with one or two Sec residues; however, only the upstream Sec
            (conserved with the single Sec residue found at the active site in
            DIO1 and DIO3) was shown to be essential for enzyme activity
            (PMID:10403186). Alternatively spliced transcript variants have
            been described for this gene. [provided by RefSeq, Oct 2018].
            
            Transcript Variant: This variant (1, also known as hDII-a)
            represents the predominant transcript and encodes two isoforms
            resulting from the use of alternative in-frame translation
            termination codons. The shorter isoform (b) with one Sec residue
            results from translation termination at the second UGA codon, while
            the longer isoform (a) with two Sec residues results from
            translation termination at an in-frame downstream UAA stop codon.
            This RefSeq represents the longer isoform (a).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            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 exon combination :: SRR1803613.248181.1,
                                           SRR1660805.88700.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1968189, SAMEA1968540
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match              :: ENST00000438257.9/
                                               ENSP00000405854.5
            protein contains selenocysteine :: PMID: 9837913, 10403186
            RefSeq Select criteria          :: based on manual assertion,
                                               conservation, expression,
                                               longest protein
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2659              AF093774.1         124-2782
            2660-4766           BC136514.1         2653-4759
            4767-6017           AC007372.4         44161-45411         c
FEATURES             Location/Qualifiers
     source          1..6017
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q31.1"
     gene            1..6017
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /note="iodothyronine deiodinase 2"
                     /db_xref="GeneID:1734"
                     /db_xref="HGNC:HGNC:2884"
                     /db_xref="MIM:601413"
     exon            1..254
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /inference="alignment:Splign:2.1.0"
     CDS             33..854
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /EC_number="1.21.99.4"
                     /note="isoform a is encoded by transcript variant 1;
                     thyroxine deiodinase, type II; type-II 5'deiodinase; type
                     2 iodothyronine deiodinase; type 2 DI; type-II
                     5'-deiodinase; deiodinase-2; deiodonase-2; selenoprotein
                     Y; deiodinase, iodothyronine type II"
                     /codon_start=1
                     /transl_except=(pos:429..431,aa:Sec)
                     /transl_except=(pos:828..830,aa:Sec)
                     /product="type II iodothyronine deiodinase isoform a"
                     /protein_id="NP_054644.1"
                     /db_xref="CCDS:CCDS45146.1"
                     /db_xref="GeneID:1734"
                     /db_xref="HGNC:HGNC:2884"
                     /db_xref="MIM:601413"
                     /translation="MGILSVDLLITLQILPVFFSNCLFLALYDSVILLKHVVLLLSRS
                     KSTRGEWRRMLTSEGLRCVWKSFLLDAYKQVKLGEDAPNSSVVHVSSTEGGDNSGNGT
                     QEKIAEGATCHLLDFASPERPLVVNFGSATUPPFTSQLPAFRKLVEEFSSVADFLLVY
                     IDEAHPSDGWAIPGDSSLSFEVKKHQNQEDRCAAAQQLLERFSLPPQCRVVADRMDNN
                     ANIAYGVAFERVCIVQRQKIAYLGGKGPFSYNLQEVRHWLEKNFSKRUKKTRLAG"
     exon            255..6017
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3015..3020
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /note="hexamer: AATAAA"
     polyA_site      3042
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
     regulatory      5697..5769
                     /regulatory_class="recoding_stimulatory_region"
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /note="SECIS_element"
                     /function="essential for recoding UGA to specify
                     selenocysteine"
     regulatory      5989..5994
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /note="hexamer: AATAAA"
     polyA_site      6017
                     /gene="DIO2"
                     /gene_synonym="5DII; D2; DIOII; SELENOY; SelY; TXDI2"
                     /note="major polyA site"
ORIGIN      
        1 gcacaaggga actgactcag gaggcagaga agatgggcat cctcagcgta gacttgctga
       61 tcacactgca aattctgcca gtttttttct ccaactgcct cttcctggct ctctatgact
      121 cggtcattct gctcaagcac gtggtgctgc tgttgagccg ctccaagtcc actcgcggag
      181 agtggcggcg catgctgacc tcagagggac tgcgctgcgt ctggaagagc ttcctcctcg
      241 atgcctacaa acaggtgaaa ttgggtgagg atgcccccaa ttccagtgtg gtgcatgtct
      301 ccagtacaga aggaggtgac aacagtggca atggtaccca ggagaagata gctgagggag
      361 ccacatgcca ccttcttgac tttgccagcc ctgagcgccc actagtggtc aactttggct
      421 cagccacttg acctcctttc acgagccagc tgccagcctt ccgcaaactg gtggaagagt
      481 tctcctcagt ggctgacttc ctgctggtct acattgatga ggctcatcca tcagatggct
      541 gggcgatacc gggggactcc tctttgtctt ttgaggtgaa gaagcaccag aaccaggaag
      601 atcgatgtgc agcagcccag cagcttctgg agcgtttctc cttgccgccc cagtgccgag
      661 ttgtggctga ccgcatggac aataacgcca acatagctta cggggtagcc tttgaacgtg
      721 tgtgcattgt gcagagacag aaaattgctt atctgggagg aaagggcccc ttctcctaca
      781 accttcaaga agtccggcat tggctggaga agaatttcag caagagatga aagaaaacta
      841 gattagctgg ttaaaggtat gattataaga gagcttattg ttttaaaaag ttatataaag
      901 gcaaggaaat taagaactga atccatattt caacagagcc ctattggctt actgaaagac
      961 aggagtttat ctatcggaag aacatgaatc tctaacagct ccatacttct ttcactactc
     1021 aaatggcatt gggctgagta agtaaccata tcacctctct tcttagtaaa aagccctatg
     1081 tgaaaagatc ccaagatgga gaggaagaaa cgctaattca gcatgtgttc attctgcatt
     1141 gagaaggaac tgatacatct gatgcatgct ttgagaccag aagaaaagac ttacctgaat
     1201 aattactaca ttagggaagc tactgtctac gttaagataa agggtattgc cttggctcta
     1261 tttggcatgg atggagccca gttggaaaat tcccaaatat tacaacaagt ccttgaaccc
     1321 aggccatgtg gttagacgtt ggtgttaagg ttagacctta tgttagagtc atttctgatg
     1381 ttccagcttc tagccatgta gtgctctcag tcttcatacc ccagaaatta ttggtatatt
     1441 tgtagatacc gagaatgatc cctcagtctg agaggttaga atgatcatct gtaatctgag
     1501 ggttaatttc taggcaggtg gagagagtgg taaaaaagaa atgaaattga caagctagga
     1561 aagaggaggc agaaagattt ggaaaattca cagagtttca cccttaagct gtagagagtg
     1621 ggtcacattt gttagccacg gaaacataga aacatacaca aggccagaaa aagaagaagg
     1681 agctcaacta aaagtggcat agagaataca catataaaaa caatatattt gtcatatgct
     1741 cctagagagg agaaaggggt gattgaaaga aaaaaaaata cttaaatatt tgtaattgtg
     1801 aggggtttct tttggaaata attacttttg aaccatgtat gtggtatgta tattttcagt
     1861 gggttaatta taccccatga tacctattaa aggaaaacca gtgggtctgg tggtgctggt
     1921 cttttcctcc ccattcctac aatttctatg tggcccaagt cattcctaat cttggtctct
     1981 atagcagtgt tctctctgaa tgctgagctg aagaaattat acgtacatac acacatacat
     2041 acatacatac aaatatatgt atatatattc tcagctgctg cgggaggtag gtaccatggc
     2101 cattcagcac agccttgatt tcctcccaaa gtaggtgagc tatagtgaag aataggtgca
     2161 aacaaacaag cttacttcca ttgcaaaata gaagaagagg aagttagaga taattctgat
     2221 caatcatttt ggaggctttg ttataaggca acccccggta tatcatggaa tttccattga
     2281 catttgaatt tggacttgga tcttcccttg gtcccattag ctgaggttta gtaatctaaa
     2341 gtccctatag tatatgatta taatgctatt ttaaaaaata tatatataaa atattttttt
     2401 ctttttaaaa tagacactat agttttaccc ataagtaata tttaaagatt atagctccca
     2461 aaagaatgga ccaaccactt tcgtatcata atttcttttt ggtaaatatg agactattat
     2521 gaaatcatag tatatgattg tatttaaagg tacaatcaaa ggatcttttg tccattccat
     2581 taataactga ataaaaaata aataaaatgg atagaaaaaa actaaagttg aaaatacatt
     2641 cttaaactag ttgtctgaat tgagaaaaga gtgagaacta ggtgtgcaag aaccaaacgt
     2701 attttatttt attttttaaa tgggagcaac atatcagtcg tgtcaccagc tggtatattg
     2761 tgtaaatatt aaagctccat tgggactgat ttttcatggc aacatcagct ttctaatgtt
     2821 ctaaattcta taaaaaccac ccacaaagaa acaaagcaaa tttcattatc taatgagttg
     2881 ctggaaaatc atattgagaa taattatttc agattcctca gttgttaact tctacattca
     2941 aggcttatct ctgcccccat tgatttttaa cctcaaaatg gtgttgagat ttacgtggaa
     3001 ccctaaagca gtaaaataaa aaacctggtt gcagcacatt cacactgttg tccttaaaat
     3061 tccccttttt tctctatgta cgataaagta acagtatgtc agataagccg gtggggggat
     3121 gagattaggc tgaggcagtg ctagtcaact ggggaaaagg atgatggaaa aatcacccag
     3181 ttgtgctata tttttaaaga aggaggtcgt ttatgtgtgc agacaattct ccctgaggtt
     3241 agcccaatgg agaaatgaag cagaggaagg aaacatagaa agacatgggc tatcagggag
     3301 gaagatgttc aatagaacat gcaagaattt ctggaagaaa ggctgtggaa gggccaatgg
     3361 agaaaatgaa tggacaaagc tcaggaatcc tacgctatgt agaatgtctt ggtgttatca
     3421 gggttaagcc tgtaattatg taacctattt atcgcaacat gaatttttat gatttcttgt
     3481 gatgtattct tttatgaaat taacaagaac tcattatttt gaggtagagg aaaatcaatg
     3541 ctttatctga tatgctgaga aattattaga ttgccaatac tcatgtgcgt ttcatgtgtt
     3601 ttataaggtt tgttcctttg aagaattgta gttcttagtc ccacagggaa atgtgtatct
     3661 atttatatat catagtataa atctatgata tatttatatc atatataaaa gtctgagttc
     3721 tctttcttag tccctaatca tgtttctccc ataggctgtg tttacatgga gctatcggtt
     3781 tagcctttta agcttcatta gcttgtctat tattgaaata gtttccaaga aattttagat
     3841 attatcataa catctgggtc tactcaaaca cttattgttt gaaagactta tgtcttggac
     3901 ctatcaaaaa ctgactttat ttattgctta gtgaaaatac tagtgggatc aacaatgatt
     3961 ttcttgaatg ggcatgaatg gagatgcccg cacagtaatg tagaaatgtt tcatacagct
     4021 attaaaatgt aactgacctc cttagaggca gattagtaac tgttcctact ttgtatagct
     4081 aagtgacagt cacttaactt acatgacttt cttttttcac attgggtctc tggtcctgtg
     4141 tcttcacctc atttatagca cgtctccttg atttttggta gtatcaactt cccagtgatc
     4201 tgttcagtta agttcttctc ccgttaacca ggaagtgctt attctctcat cacagtggga
     4261 agaatagcct attgtctttc attttgcctg agtgtatttt actatttggg ctctgaaata
     4321 aaaattatga aatatggtga ggtcacatgt tggtgctgcc ttgctgcata aaattctaga
     4381 gggcaggtta gagacagtat gtatgccttc gggaaaattc aaaggtggat tacaaggtgt
     4441 cctcagcatg ccctatggcc tatgtgcgaa gcaagaagaa ttgactgatt tacaggactt
     4501 ctctttatgt caatcttaag aggatggatg aatctggaca tttgttccac ccgacctctg
     4561 actgatggtt tggaaaataa ctttaattag gatcatatga ccattgaaaa aggaaaaatg
     4621 tagactctga cttccgtccc actgaaggat taatgaaaac ctttactagc atttagagct
     4681 tttcagaaca tccccactgt catgtgtctc agcagtggag actgcaagta aggcttttaa
     4741 ttttaggagg tttttttttt tttttttttt tccctaaatg gtatggccaa aagtcagagt
     4801 taaaatatat atagttagat tccaacttcc tccttcactc taaaaataga atccaaaccc
     4861 actcttcata tatgcttcca gaatggggct taagtaccaa tctctgcttt gcaatgggca
     4921 caatcttggt catgtcctga ggctctctaa gaaaagagag gatctaggat gggagagcta
     4981 gaaagttgct aactgggaag aacaaggccc tgagggcttg gtctaccaat ctgggaagat
     5041 ttgaaaacaa acttctcgca actgaaggaa ggctgaaggc tgctgcaagt cattgagtga
     5101 ctttaggatg agcaaaacat tgggccactt cctaatgccc tatgtgtata gtaccagaag
     5161 caaggtctca gacttaacag acccagctct gttccaaggt gagtctgaac caatagaaag
     5221 caaacatgtg cagatatcca aacaagactg ctcatgcaag tcggggctgg ctacccgtct
     5281 taggcagcaa cagcagagct ccagggagct tattcaatat ttactgagac ttcgaagacc
     5341 cagcagatgt ttaatgaagt cactattttg gctcaaaccc tccacttctc cccctcccct
     5401 caaaaagcca acaggtaaac acataaatga aagaaaccca cagaagggga tgggaaataa
     5461 agaaaattct ctcaagactt ctccaggccc atgtcactgg tcagcgtggt ttttatgtgt
     5521 attaggattg ggggatgtga agaaataagt atccagtact ttataaccaa agcaattaaa
     5581 tgatattggg tagggaatgt tggccagttt tgtttagttt tgcatcacat tgtcaccaga
     5641 ctcactagcc caagtaatcg ggcgcccgaa gagggagaca gagatgtgca gagttgacca
     5701 gtgtgcggat gataactact gacgaaagag tcatcgactc agttagtggt tggatgtagt
     5761 cacattagtt tgcctctccc catctttgtc tccctggcaa ggagaatatg cgggacatga
     5821 tgctaagagt cctgggtaaa tgtggtgaga atgcacgcgt gcatatgcta cacatatgtg
     5881 cttctcagtt gcagaaaatg aactgctttg ggagattatc agtagaaaga gtgttatcat
     5941 attggtgctg agtgctatgt gtgcttatac aatttgttct tgtattttaa taaactttga
     6001 ataaaagaat aaagcta
//
