LOCUS       NM_001206744            4085 bp    mRNA    linear   PRI 11-JUN-2024
DEFINITION  Homo sapiens thyroid peroxidase (TPO), transcript variant 6, mRNA.
ACCESSION   NM_001206744
VERSION     NM_001206744.2
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 4085)
  AUTHORS   Iwasaki,H., Suwanai,H., Yakou,F., Sakai,H., Ishii,K., Hara,N.,
            Buckle,A.M., Kanekura,K., Miyagi,T., Narumi,S. and Suzuki,R.
  TITLE     Disulfide Bonds of Thyroid Peroxidase Are Critical Elements for
            Subcellular Localization, Proteasome-Dependent Degradation, and
            Enzyme Activity
  JOURNAL   Thyroid 34 (5), 659-667 (2024)
   PUBMED   38482822
  REMARK    GeneRIF: Disulfide Bonds of Thyroid Peroxidase Are Critical
            Elements for Subcellular Localization, Proteasome-Dependent
            Degradation, and Enzyme Activity.
REFERENCE   2  (bases 1 to 4085)
  AUTHORS   Lacka,K., Maciejewski,A., Jarecki,P., Herman,W., Lacki,J.K.,
            Zaba,R. and Kowalczyk,M.J.
  TITLE     Is There a Link between Thyroid Peroxidase Gene Promoter
            Polymorphisms and Autoimmune Thyroiditis in the Polish Population?
  JOURNAL   Int J Mol Sci 25 (6), 3312 (2024)
   PUBMED   38542286
  REMARK    GeneRIF: Is There a Link between Thyroid Peroxidase Gene Promoter
            Polymorphisms and Autoimmune Thyroiditis in the Polish Population?
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 4085)
  AUTHORS   Naqvi,S.F., Yildiz-Bolukbasi,E., Afzal,M., Nalbant,G., Mumtaz,S.,
            Tolun,A. and Malik,S.
  TITLE     Homozygous Mutations in Thyroid Peroxidase (TPO) in Hypothyroidism
            with Intellectual Disability, Developmental Delay, and Hearing and
            Ocular Anomalies in Two Families: Severe Manifestation of Untreated
            TPO-deficiency Poses a Diagnostic Dilemma
  JOURNAL   Yale J Biol Med 96 (3), 347-365 (2023)
   PUBMED   37780999
  REMARK    GeneRIF: Homozygous Mutations in Thyroid Peroxidase (TPO) in
            Hypothyroidism with Intellectual Disability, Developmental Delay,
            and Hearing and Ocular Anomalies in Two Families: Severe
            Manifestation of Untreated TPO-deficiency Poses a Diagnostic
            Dilemma.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4085)
  AUTHORS   Ferrand,M., Le Fourn,V. and Franc,J.L.
  TITLE     Increasing diversity of human thyroperoxidase generated by
            alternative splicing. Characterized by molecular cloning of new
            transcripts with single- and multispliced mRNAs
  JOURNAL   J Biol Chem 278 (6), 3793-3800 (2003)
   PUBMED   12454013
  REMARK    GeneRIF: investigation of diversity generated by alternative
            splicing
REFERENCE   5  (bases 1 to 4085)
  AUTHORS   Abramowicz,M.J., Targovnik,H.M., Varela,V., Cochaux,P., Krawiec,L.,
            Pisarev,M.A., Propato,F.V., Juvenal,G., Chester,H.A. and Vassart,G.
  TITLE     Identification of a mutation in the coding sequence of the human
            thyroid peroxidase gene causing congenital goiter
  JOURNAL   J Clin Invest 90 (4), 1200-1204 (1992)
   PUBMED   1401057
REFERENCE   6  (bases 1 to 4085)
  AUTHORS   Lagorce,J.F., Thomes,J.C., Catanzano,G., Buxeraud,J., Raby,M. and
            Raby,C.
  TITLE     Formation of molecular iodine during oxidation of iodide by the
            peroxidase/H2O2 system. Implications for antithyroid therapy
  JOURNAL   Biochem Pharmacol 42 Suppl, S89-S92 (1991)
   PUBMED   1722671
REFERENCE   7  (bases 1 to 4085)
  AUTHORS   Kimura,S., Hong,Y.S., Kotani,T., Ohtaki,S. and Kikkawa,F.
  TITLE     Structure of the human thyroid peroxidase gene: comparison and
            relationship to the human myeloperoxidase gene
  JOURNAL   Biochemistry 28 (10), 4481-4489 (1989)
   PUBMED   2548579
REFERENCE   8  (bases 1 to 4085)
  AUTHORS   Magnusson,R.P., Chazenbalk,G.D., Gestautas,J., Seto,P., Filetti,S.,
            DeGroot,L.J. and Rapoport,B.
  TITLE     Molecular cloning of the complementary deoxyribonucleic acid for
            human thyroid peroxidase
  JOURNAL   Mol Endocrinol 1 (11), 856-861 (1987)
   PUBMED   3153466
REFERENCE   9  (bases 1 to 4085)
  AUTHORS   Kimura,S., Kotani,T., McBride,O.W., Umeki,K., Hirai,K., Nakayama,T.
            and Ohtaki,S.
  TITLE     Human thyroid peroxidase: complete cDNA and protein sequence,
            chromosome mapping, and identification of two alternately spliced
            mRNAs
  JOURNAL   Proc Natl Acad Sci U S A 84 (16), 5555-5559 (1987)
   PUBMED   3475693
REFERENCE   10 (bases 1 to 4085)
  AUTHORS   Degroot,L.J. and Niepomniszcze,H.
  TITLE     Biosynthesis of thyroid hormone: basic and clinical aspects
  JOURNAL   Metabolism 26 (6), 665-718 (1977)
   PUBMED   67547
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC095448.1, Y00406.1 and
            AC141930.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 1, 2019 this sequence version replaced NM_001206744.1.
            
            Summary: This gene encodes a membrane-bound glycoprotein. The
            encoded protein acts as an enzyme and plays a central role in
            thyroid gland function. The protein functions in the iodination of
            tyrosine residues in thyroglobulin and phenoxy-ester formation
            between pairs of iodinated tyrosines to generate the thyroid
            hormones, thyroxine and triiodothyronine. Mutations in this gene
            are associated with several disorders of thyroid hormonogenesis,
            including congenital hypothyroidism, congenital goiter, and thyroid
            hormone organification defect IIA. Multiple transcript variants
            encoding distinct isoforms have been identified for this gene, but
            the full-length nature of some variants has not been determined.
            [provided by RefSeq, May 2011].
            
            Transcript Variant: This variant (6) lacks a segment in the 5' UTR
            and encodes the same isoform (a, also known as TPO1), compared to
            variant 1.
            
            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 :: BC095448.1, Y00406.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA2144120, SAMEA2145240
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000329066.9/ ENSP00000329869.4
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-83                BC095448.1         1-83
            84-292              Y00406.1           40-248
            293-2966            BC095448.1         293-2966
            2967-4085           AC141930.2         1301-2419
FEATURES             Location/Qualifiers
     source          1..4085
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p25.3"
     gene            1..4085
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /note="thyroid peroxidase"
                     /db_xref="GeneID:7173"
                     /db_xref="HGNC:HGNC:12015"
                     /db_xref="MIM:606765"
     exon            1..83
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            84..178
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     CDS             85..2886
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /EC_number="1.11.1.8"
                     /note="isoform a precursor is encoded by transcript
                     variant 6; thyroperoxidase; thyroid microsomal antigen"
                     /codon_start=1
                     /product="thyroid peroxidase isoform a precursor"
                     /protein_id="NP_001193673.1"
                     /db_xref="CCDS:CCDS1643.1"
                     /db_xref="GeneID:7173"
                     /db_xref="HGNC:HGNC:12015"
                     /db_xref="MIM:606765"
                     /translation="MRALAVLSVTLVMACTEAFFPFISRGKELLWGKPEESRVSSVLE
                     ESKRLVDTAMYATMQRNLKKRGILSPAQLLSFSKLPEPTSGVIARAAEIMETSIQAMK
                     RKVNLKTQQSQHPTDALSEDLLSIIANMSGCLPYMLPPKCPNTCLANKYRPITGACNN
                     RDHPRWGASNTALARWLPPVYEDGFSQPRGWNPGFLYNGFPLPPVREVTRHVIQVSNE
                     VVTDDDRYSDLLMAWGQYIDHDIAFTPQSTSKAAFGGGADCQMTCENQNPCFPIQLPE
                     EARPAAGTACLPFYRSSAACGTGDQGALFGNLSTANPRQQMNGLTSFLDASTVYGSSP
                     ALERQLRNWTSAEGLLRVHARLRDSGRAYLPFVPPRAPAACAPEPGIPGETRGPCFLA
                     GDGRASEVPSLTALHTLWLREHNRLAAALKALNAHWSADAVYQEARKVVGALHQIITL
                     RDYIPRILGPEAFQQYVGPYEGYDSTANPTVSNVFSTAAFRFGHATIHPLVRRLDASF
                     QEHPDLPGLWLHQAFFSPWTLLRGGGLDPLIRGLLARPAKLQVQDQLMNEELTERLFV
                     LSNSSTLDLASINLQRGRDHGLPGYNEWREFCGLPRLETPADLSTAIASRSVADKILD
                     LYKHPDNIDVWLGGLAENFLPRARTGPLFACLIGKQMKALRDGDWFWWENSHVFTDAQ
                     RRELEKHSLSRVICDNTGLTRVPMDAFQVGKFPEDFESCDSITGMNLEAWRETFPQDD
                     KCGFPESVENGDFVHCEESGRRVLVYSCRHGYELQGREQLTCTQEGWDFQPPLCKDVN
                     ECADGAHPPCHASARCRNTKGGFQCLCADPYELGDDGRTCVDSGRLPRVTWISMSLAA
                     LLIGGFAGLTSTVICRWTRTGTKSTLPISETGGGTPELRCGKHQAVGTSPQRAAAQDS
                     EQESAGMEGRDTHRLPRAL"
     exon            179..263
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            264..433
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            434..566
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            567..696
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            697..903
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            904..1422
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            1423..1681
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            1682..1852
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            1853..2090
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2091..2299
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2300..2470
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2471..2602
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2603..2702
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2703..2832
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     exon            2833..4085
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3043..3048
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /note="hexamer: AATAAA"
     polyA_site      3061
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /note="major polyA site"
     regulatory      4063..4068
                     /regulatory_class="polyA_signal_sequence"
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /note="hexamer: ATTAAA"
     polyA_site      4085
                     /gene="TPO"
                     /gene_synonym="MSA; TDH2A; TPX"
                     /note="major polyA site"
ORIGIN      
        1 aaggcaatta aggcgcccat ttcagaagag ttacagccgt gaaaattact cagcagtgca
       61 gttggctgag aagaggaaaa aagaatgaga gcgctcgctg tgctgtctgt cacgctggtt
      121 atggcctgca cagaagcctt cttccccttc atctcgagag ggaaagaact cctttgggga
      181 aagcctgagg agtctcgtgt ctctagcgtc ttggaggaaa gcaagcgcct ggtggacacc
      241 gccatgtacg ccacgatgca gagaaacctc aagaaaagag gaatcctttc tccagctcag
      301 cttctgtctt tttccaaact tcctgagcca acaagcggag tgattgcccg agcagcagag
      361 ataatggaaa catcaataca agcgatgaaa agaaaagtca acctgaaaac tcaacaatca
      421 cagcatccaa cggatgcttt atcagaagat ctgctgagca tcattgcaaa catgtctgga
      481 tgtctccctt acatgctgcc cccaaaatgc ccaaacactt gcctggcgaa caaatacagg
      541 cccatcacag gagcttgcaa caacagagac caccccagat ggggcgcctc caacacggcc
      601 ctggcacgat ggctccctcc agtctatgag gacggcttca gtcagccccg aggctggaac
      661 cccggcttct tgtacaacgg gttcccactg cccccggtcc gggaggtgac aagacatgtc
      721 attcaagttt caaatgaggt tgtcacagat gatgaccgct attctgacct cctgatggca
      781 tggggacaat acatcgacca cgacatcgcg ttcacaccac agagcaccag caaagctgcc
      841 ttcgggggag gggctgactg ccagatgact tgtgagaacc aaaacccatg ttttcccata
      901 caactcccgg aggaggcccg gccggccgcg ggcaccgcct gtctgccctt ctaccgctct
      961 tcggccgcct gcggcaccgg ggaccaaggc gcgctctttg ggaacctgtc cacggccaac
     1021 ccgcggcagc agatgaacgg gttgacctcg ttcctggacg cgtccaccgt gtatggcagc
     1081 tccccggccc tagagaggca gctgcggaac tggaccagtg ccgaagggct gctccgcgtc
     1141 cacgcgcgcc tccgggactc cggccgcgcc tacctgccct tcgtgccgcc acgcgcgcct
     1201 gcggcctgtg cgcccgagcc cggcatcccc ggagagaccc gcgggccctg cttcctggcc
     1261 ggagacggcc gcgccagcga ggtcccctcc ctgacggcac tgcacacgct gtggctgcgc
     1321 gagcacaacc gcctggccgc ggcgctcaag gccctcaatg cgcactggag cgcggacgcc
     1381 gtgtaccagg aggcgcgcaa ggtcgtgggc gctctgcacc agatcatcac cctgagggat
     1441 tacatcccca ggatcctggg acccgaggcc ttccagcagt acgtgggtcc ctatgaaggc
     1501 tatgactcca ccgccaaccc cactgtgtcc aacgtgttct ccacagccgc cttccgcttc
     1561 ggccatgcca cgatccaccc gctggtgagg aggctggacg ccagcttcca ggagcacccc
     1621 gacctgcccg ggctgtggct gcaccaggct ttcttcagcc catggacatt actccgtgga
     1681 ggtggtttgg acccactaat acgaggcctt cttgcaagac cagccaaact gcaggtgcag
     1741 gatcagctga tgaacgagga gctgacggaa aggctctttg tgctgtccaa ttccagcacc
     1801 ttggatctgg cgtccatcaa cctgcagagg ggccgggacc acgggctgcc aggttacaat
     1861 gagtggaggg agttctgcgg cctgcctcgc ctggagaccc ccgctgacct gagcacagcc
     1921 atcgccagca ggagcgtggc cgacaagatc ctggacttgt acaagcatcc tgacaacatc
     1981 gatgtctggc tgggaggctt agctgaaaac ttcctcccca gggctcggac agggcccctg
     2041 tttgcctgtc tcattgggaa gcagatgaag gctctgcggg acggtgactg gttttggtgg
     2101 gagaacagcc acgtcttcac ggatgcacag aggcgtgagc tggagaagca ctccctgtct
     2161 cgggtcatct gtgacaacac tggcctcacc agggtgccca tggatgcctt ccaagtcggc
     2221 aaattccccg aagactttga gtcttgtgac agcatcactg gcatgaacct ggaggcctgg
     2281 agggaaacct ttcctcaaga cgacaagtgt ggcttcccag agagcgtgga gaatggggac
     2341 tttgtgcact gtgaggagtc tgggaggcgc gtgctggtgt attcctgccg gcacgggtat
     2401 gagctccaag gccgggagca gctcacttgc acccaggaag gatgggattt ccagcctccc
     2461 ctctgcaaag atgtgaacga gtgtgcagac ggtgcccacc ccccctgcca cgcctctgcg
     2521 aggtgcagaa acaccaaagg cggcttccag tgtctctgcg cggaccccta cgagttagga
     2581 gacgatggga gaacctgcgt agactccggg aggctccctc gggtgacttg gatctccatg
     2641 tcgctggctg ctctgctgat cggaggcttc gcaggtctca cctcgacggt gatttgcagg
     2701 tggacacgca ctggcactaa atccacactg cccatctcgg agacaggcgg aggaactccc
     2761 gagctgagat gcggaaagca ccaggccgta gggacctcac cgcagcgggc cgcagctcag
     2821 gactcggagc aggagagtgc tgggatggaa ggccgggata ctcacaggct gccgagagcc
     2881 ctctgagggc aaagtggcag gacactgcag aacagcttca tgttcccaaa atcaccgtac
     2941 gactcttttc caaacacagg caaatccgaa atcagcagga cgactgtttt cccaacacgg
     3001 gtaaatctag taccatgtcg tagttactct caggcatgga tgaataaatg ttatagctgc
     3061 atttgtctgg ccttttcttg taaacattgc ctgatttgtt ccttctgggg ctttgccatt
     3121 aaaatgtatt tacagattac acatctttat tttgtgaacc ctggaaacac cactcttgca
     3181 atcctcctgt ctccaccttc tggcatctct gatgccgtgc tcgtctgcac tctgccccgg
     3241 cggtccctcc agcactggtt tttccacacc ccctgcccat caccaggtgt ccacagggcc
     3301 tacatctggc ttccctcttc tcctgggaag agcactcctg gcttcctgca gggccggtgg
     3361 gaggaggaaa gtgattctga gggagaggct ggagccttaa ggaccaacaa ggcaaagtga
     3421 cttgtctcat cctccagaga ttcaccaaca catgagcctc agaccccagg cttctgcctc
     3481 cagcagccgc cctgccgcac actgctctta ctcctcctta taccctcact cacggggaac
     3541 acagcccagt gatcccggag gaaactcact ccctccctga ctcaacaagg cagtctcggg
     3601 ggcaccgtta gccacgcgac cctgtaaagc tgccgtcctc atttcacatg tgaagcagct
     3661 gaattccaga gtgctgggtc ccagcccagg cagccctcag cctcacgcaa ggcaatagtt
     3721 aggagtcctt cggcattgaa agcaaactca gacacatctg acctggagtt ctacctgcac
     3781 taagagaaga gagtggtaac taattcatgg ataaaacaga ccatcgaggc agcactgaat
     3841 gatctcaccc acgaatgaca acagtggcac aggagggcta tgaacatttt gcttcaggat
     3901 gttttatttc gctctactgt tatgtagaga aagcatggtt tgctttttat aacttttgtg
     3961 acccaaaaat accagactgt tgttttccct aggtgccagg ccatcctgtt ctgtgtgttc
     4021 ccaaactctt agttttgttc atgtaaaact catgatttca taattaaaac aatattaaaa
     4081 taaaa
//
