Thyroid peroxidase

Details

Name
Thyroid peroxidase
Synonyms
  • 1.11.1.8
  • TPO
Gene Name
TPO
Organism
Humans
Amino acid sequence
>lcl|BSEQ0037030|Thyroid peroxidase
MRALAVLSVTLVMACTEAFFPFISRGKELLWGKPEESRVSSVLEESKRLVDTAMYATMQR
NLKKRGILSPAQLLSFSKLPEPTSGVIARAAEIMETSIQAMKRKVNLKTQQSQHPTDALS
EDLLSIIANMSGCLPYMLPPKCPNTCLANKYRPITGACNNRDHPRWGASNTALARWLPPV
YEDGFSQPRGWNPGFLYNGFPLPPVREVTRHVIQVSNEVVTDDDRYSDLLMAWGQYIDHD
IAFTPQSTSKAAFGGGADCQMTCENQNPCFPIQLPEEARPAAGTACLPFYRSSAACGTGD
QGALFGNLSTANPRQQMNGLTSFLDASTVYGSSPALERQLRNWTSAEGLLRVHARLRDSG
RAYLPFVPPRAPAACAPEPGIPGETRGPCFLAGDGRASEVPSLTALHTLWLREHNRLAAA
LKALNAHWSADAVYQEARKVVGALHQIITLRDYIPRILGPEAFQQYVGPYEGYDSTANPT
VSNVFSTAAFRFGHATIHPLVRRLDASFQEHPDLPGLWLHQAFFSPWTLLRGGGLDPLIR
GLLARPAKLQVQDQLMNEELTERLFVLSNSSTLDLASINLQRGRDHGLPGYNEWREFCGL
PRLETPADLSTAIASRSVADKILDLYKHPDNIDVWLGGLAENFLPRARTGPLFACLIGKQ
MKALRDGDWFWWENSHVFTDAQRRELEKHSLSRVICDNTGLTRVPMDAFQVGKFPEDFES
CDSITGMNLEAWRETFPQDDKCGFPESVENGDFVHCEESGRRVLVYSCRHGYELQGREQL
TCTQEGWDFQPPLCKDVNECADGAHPPCHASARCRNTKGGFQCLCADPYELGDDGRTCVD
SGRLPRVTWISMSLAALLIGGFAGLTSTVICRWTRTGTKSTLPISETGGGTPELRCGKHQ
AVGTSPQRAAAQDSEQESAGMEGRDTHRLPRAL
Number of residues
933
Molecular Weight
102961.63
Theoretical pI
6.75
GO Classification
Functions
calcium ion binding / heme binding / iodide peroxidase activity / peroxidase activity
Processes
cellular nitrogen compound metabolic process / cellular response to nitric oxide / embryonic hemopoiesis / hormone biosynthetic process / hydrogen peroxide catabolic process / response to lipid / small molecule metabolic process / thyroid hormone generation
Components
cell surface / extracellular space / integral component of plasma membrane / mitochondrion / plasma membrane
General Function
Peroxidase activity
Specific Function
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Pfam Domain Function
Transmembrane Regions
847-871
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0010357|Thyroid peroxidase (TPO)
ATGAGAGCGCTCGCTGTGCTGTCTGTCACGCTGGTTATGGCCTGCACAGAAGCCTTCTTC
CCCTTCATCTCGAGAGGGAAAGAACTCCTTTGGGGAAAGCCTGAGGAGTCTCGTGTCTCT
AGCGTCTTGGAGGAAAGCAAGCGCCTGGTGGACACCGCCATGTACGCCACGATGCAGAGA
AACCTCAAGAAAAGAGGAATCCTTTCTCCAGCTCAGCTTCTGTCTTTTTCCAAACTTCCT
GAGCCAACAAGCGGAGTGATTGCCCGAGCAGCAGAGATAATGGAAACATCAATACAAGCG
ATGAAAAGAAAAGTCAACCTGAAAACTCAACAATCACAGCATCCAACGGATGCTTTATCA
GAAGATCTGCTGAGCATCATTGCAAACATGTCTGGATGTCTCCCTTACATGCTGCCCCCA
AAATGCCCAAACACTTGCCTGGCGAACAAATACAGGCCCATCACAGGAGCTTGCAACAAC
AGAGACCACCCCAGATGGGGCGCCTCCAACACGGCCCTGGCACGATGGCTCCCTCCAGTC
TATGAGGACGGCTTCAGTCAGCCCCGAGGCTGGAACCCCGGCTTCTTGTACAACGGGTTC
CCACTGCCCCCGGTCCGGGAGGTGACAAGACATGTCATTCAAGTTTCAAATGAGGTTGTC
ACAGATGATGACCGCTATTCTGACCTCCTGATGGCATGGGGACAATACATCGACCACGAC
ATCGCGTTCACACCACAGAGCACCAGCAAAGCTGCCTTCGGGGGAGGGGCTGACTGCCAG
ATGACTTGTGAGAACCAAAACCCATGTTTTCCCATACAACTCCCGGAGGAGGCCCGGCCG
GCCGCGGGCACCGCCTGTCTGCCCTTCTACCGCTCTTCGGCCGCCTGCGGCACCGGGGAC
CAAGGCGCGCTCTTTGGGAACCTGTCCACGGCCAACCCGCGGCAGCAGATGAACGGGTTG
ACCTCGTTCCTGGACGCGTCCACCGTGTATGGCAGCTCCCCGGCCCTAGAGAGGCAGCTG
CGGAACTGGACCAGTGCCGAAGGGCTGCTCCGCGTCCACGCGCGCCTCCGGGACTCCGGC
CGCGCCTACCTGCCCTTCGTGCCGCCACGCGCGCCTGCGGCCTGTGCGCCCGAGCCCGGC
ATCCCCGGAGAGACCCGCGGGCCCTGCTTCCTGGCCGGAGACGGCCGCGCCAGCGAGGTC
CCCTCCCTGACGGCACTGCACACGCTGTGGCTGCGCGAGCACAACCGCCTGGCCGCGGCG
CTCAAGGCCCTCAATGCGCACTGGAGCGCGGACGCCGTGTACCAGGAGGCGCGCAAGGTC
GTGGGCGCTCTGCACCAGATCATCACCCTGAGGGATTACATCCCCAGGATCCTGGGACCC
GAGGCCTTCCAGCAGTACGTGGGTCCCTATGAAGGCTATGACTCCACCGCCAACCCCACT
GTGTCCAACGTGTTCTCCACAGCCGCCTTCCGCTTCGGCCATGCCACGATCCACCCGCTG
GTGAGGAGGCTGGACGCCAGCTTCCAGGAGCACCCCGACCTGCCCGGGCTGTGGCTGCAC
CAGGCTTTCTTCAGCCCATGGACATTACTCCGTGGAGGTGGTTTGGACCCACTAATACGA
GGCCTTCTTGCAAGACCAGCCAAACTGCAGGTGCAGGATCAGCTGATGAACGAGGAGCTG
ACGGAAAGGCTCTTTGTGCTGTCCAATTCCAGCACCTTGGATCTGGCGTCCATCAACCTG
CAGAGGGGCCGGGACCACGGGCTGCCAGGTTACAATGAGTGGAGGGAGTTCTGCGGCCTG
CCTCGCCTGGAGACCCCCGCTGACCTGAGCACAGCCATCGCCAGCAGGAGCGTGGCCGAC
AAGATCCTGGACTTGTACAAGCATCCTGACAACATCGATGTCTGGCTGGGAGGCTTAGCT
GAAAACTTCCTCCCCAGGGCTCGGACAGGGCCCCTGTTTGCCTGTCTCATTGGGAAGCAG
ATGAAGGCTCTGCGGGACGGTGACTGGTTTTGGTGGGAGAACAGCCACGTCTTCACGGAT
GCACAGAGGCGTGAGCTGGAGAAGCACTCCCTGTCTCGGGTCATCTGTGACAACACTGGC
CTCACCAGGGTGCCCATGGATGCCTTCCAAGTCGGCAAATTCCCCGAAGACTTTGAGTCT
TGTGACAGCATCACTGGCATGAACCTGGAGGCCTGGAGGGAAACCTTTCCTCAAGACGAC
AAGTGTGGCTTCCCAGAGAGCGTGGAGAATGGGGACTTTGTGCACTGTGAGGAGTCTGGG
AGGCGCGTGCTGGTGTATTCCTGCCGGCACGGGTATGAGCTCCAAGGCCGGGAGCAGCTC
ACTTGCACCCAGGAAGGATGGGATTTCCAGCCTCCCCTCTGCAAAGATGTGAACGAGTGT
GCAGACGGTGCCCACCCCCCCTGCCACGCCTCTGCGAGGTGCAGAAACACCAAAGGCGGC
TTCCAGTGTCTCTGCGCGGACCCCTACGAGTTAGGAGACGATGGGAGAACCTGCGTAGAC
TCCGGGAGGCTCCCTCGGGTGACTTGGATCTCCATGTCGCTGGCTGCTCTGCTGATCGGA
GGCTTCGCAGGTCTCACCTCGACGGTGATTTGCAGGTGGACACGCACTGGCACTAAATCC
ACACTGCCCATCTCGGAGACAGGCGGAGGAACTCCCGAGCTGAGATGCGGAAAGCACCAG
GCCGTAGGGACCTCACCGCAGCGGGCCGCAGCTCAGGACTCGGAGCAGGAGAGTGCTGGG
ATGGAAGGCCGGGATACTCACAGGCTGCCGAGAGCCCTCTGA
Chromosome Location
2
Locus
2p25
External Identifiers
ResourceLink
UniProtKB IDP07202
UniProtKB Entry NamePERT_HUMAN
GenBank Protein ID339867
GenBank Gene IDJ02969
GenAtlas IDTPO
HGNC IDHGNC:12015
General References
  1. Kimura S, Kotani T, McBride OW, Umeki K, Hirai K, Nakayama T, Ohtaki S: Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5555-9. [Article]
  2. Libert F, Ruel J, Ludgate M, Swillens S, Alexander N, Vassart G, Dinsart C: Complete nucleotide sequence of the human thyroperoxidase-microsomal antigen cDNA. Nucleic Acids Res. 1987 Aug 25;15(16):6735. [Article]
  3. Kimura S, Hong YS, Kotani T, Ohtaki S, Kikkawa F: Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene. Biochemistry. 1989 May 16;28(10):4481-9. [Article]
  4. Barnett PS, Banga JP, Watkins J, Huang GC, Gluckman DR, Page MJ, McGregor AM: Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2. Nucleic Acids Res. 1990 Feb 11;18(3):670. [Article]
  5. Ferrand M, Le Fourn V, Franc JL: Increasing diversity of human thyroperoxidase generated by alternative splicing. Characterized by molecular cloning of new transcripts with single- and multispliced mRNAs. J Biol Chem. 2003 Feb 7;278(6):3793-800. Epub 2002 Nov 25. [Article]
  6. Seto P, Hirayu H, Magnusson RP, Gestautas J, Portmann L, DeGroot LJ, Rapoport B: Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase. J Clin Invest. 1987 Oct;80(4):1205-8. [Article]
  7. Zanelli E, Henry M, Charvet B, Malthiery Y: Evidence for an alternate splicing in the thyroperoxidase messenger from patients with Graves' disease. Biochem Biophys Res Commun. 1990 Jul 31;170(2):735-41. [Article]
  8. Wang D, De Deken X, Milenkovic M, Song Y, Pirson I, Dumont JE, Miot F: Identification of a novel partner of duox: EFP1, a thioredoxin-related protein. J Biol Chem. 2005 Jan 28;280(4):3096-103. Epub 2004 Nov 22. [Article]
  9. Bikker H, Vulsma T, Baas F, de Vijlder JJ: Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis. Hum Mutat. 1995;6(1):9-16. [Article]
  10. Bikker H, Baas F, De Vijlder JJ: Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects. J Clin Endocrinol Metab. 1997 Feb;82(2):649-53. [Article]
  11. Santos CL, Bikker H, Rego KG, Nascimento AC, Tambascia M, De Vijlder JJ, Medeiros-Neto G: A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect. Clin Endocrinol (Oxf). 1999 Aug;51(2):165-72. [Article]
  12. Pannain S, Weiss RE, Jackson CE, Dian D, Beck JC, Sheffield VC, Cox N, Refetoff S: Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping. J Clin Endocrinol Metab. 1999 Mar;84(3):1061-71. [Article]
  13. Kotani T, Umeki K, Yamamoto I, Maesaka H, Tachibana K, Ohtaki S: A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect. J Endocrinol. 1999 Feb;160(2):267-73. [Article]
  14. Bakker B, Bikker H, Vulsma T, de Randamie JS, Wiedijk BM, De Vijlder JJ: Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update). J Clin Endocrinol Metab. 2000 Oct;85(10):3708-12. [Article]
  15. Ambrugger P, Stoeva I, Biebermann H, Torresani T, Leitner C, Gruters A: Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism. Eur J Endocrinol. 2001 Jul;145(1):19-24. [Article]
  16. Umeki K, Kotani T, Kawano J, Suganuma T, Yamamoto I, Aratake Y, Furujo M, Ichiba Y: Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism. Eur J Endocrinol. 2002 Apr;146(4):491-8. [Article]
  17. Niu DM, Hwang B, Chu YK, Liao CJ, Wang PL, Lin CY: High prevalence of a novel mutation (2268 insT) of the thyroid peroxidase gene in Taiwanese patients with total iodide organification defect, and evidence for a founder effect. J Clin Endocrinol Metab. 2002 Sep;87(9):4208-12. [Article]
  18. Wu JY, Shu SG, Yang CF, Lee CC, Tsai FJ: Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations. J Endocrinol. 2002 Mar;172(3):627-35. [Article]
  19. Calaciura F, Miscio G, Coco A, Leonardi D, Cisternino C, Regalbuto C, Bozzali M, Maiorana R, Ranieri A, Carta A, Buscema M, Trischitta V, Sava L, Tassi V: Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach. Thyroid. 2002 Nov;12(11):945-51. [Article]
  20. Kotani T, Umeki K, Kawano J, Suganuma T, Hishinuma A, Ieiri T, Harada S: Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings. Clin Endocrinol (Oxf). 2003 Aug;59(2):198-206. [Article]
  21. Rivolta CM, Esperante SA, Gruneiro-Papendieck L, Chiesa A, Moya CM, Domene S, Varela V, Targovnik HM: Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect. Hum Mutat. 2003 Sep;22(3):259. [Article]
  22. Fugazzola L, Cerutti N, Mannavola D, Vannucchi G, Fallini C, Persani L, Beck-Peccoz P: Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect. J Clin Endocrinol Metab. 2003 Jul;88(7):3264-71. [Article]
  23. Tajima T, Tsubaki J, Fujieda K: Two novel mutations in the thyroid peroxidase gene with goitrous hypothyroidism. Endocr J. 2005 Oct;52(5):643-5. [Article]
  24. Pfarr N, Borck G, Turk A, Napiontek U, Keilmann A, Muller-Forell W, Kopp P, Pohlenz J: Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes. J Clin Endocrinol Metab. 2006 Jul;91(7):2678-81. Epub 2006 May 9. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00389Carbimazoleapproved, investigationalyesinhibitorDetails
DB00550Propylthiouracilapproved, investigationalyesinhibitorDetails
DB00763MethimazoleapprovedyessubstrateinhibitorDetails
DB00509Dextrothyroxineapproved, investigationalunknownDetails
DB114962-mercaptobenzothiazoleapproved, experimental, vet_approvedunknowninhibitorDetails
DB11085ResorcinolapprovedunknownDetails
DB08604Triclosanapproved, investigationalunknownweak inhibitorDetails
DB05382Iodineapproved, investigationalunknownsubstrateDetails