| IED ID | IndEnz0018000712 |
| Enzyme Type ID | peroxidase000712 |
| Protein Name |
Thyroid peroxidase TPO EC 1.11.1.8 |
| Gene Name | TPO |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MRALAVLSVTLVMACTEAFFPFISRGKELLWGKPEESRVSSVLEESKRLVDTAMYATMQRNLKKRGILSPAQLLSFSKLPEPTSGVIARAAEIMETSIQAMKRKVNLKTQQSQHPTDALSEDLLSIIANMSGCLPYMLPPKCPNTCLANKYRPITGACNNRDHPRWGASNTALARWLPPVYEDGFSQPRGWNPGFLYNGFPLPPVREVTRHVIQVSNEVVTDDDRYSDLLMAWGQYIDHDIAFTPQSTSKAAFGGGADCQMTCENQNPCFPIQLPEEARPAAGTACLPFYRSSAACGTGDQGALFGNLSTANPRQQMNGLTSFLDASTVYGSSPALERQLRNWTSAEGLLRVHARLRDSGRAYLPFVPPRAPAACAPEPGIPGETRGPCFLAGDGRASEVPSLTALHTLWLREHNRLAAALKALNAHWSADAVYQEARKVVGALHQIITLRDYIPRILGPEAFQQYVGPYEGYDSTANPTVSNVFSTAAFRFGHATIHPLVRRLDASFQEHPDLPGLWLHQAFFSPWTLLRGGGLDPLIRGLLARPAKLQVQDQLMNEELTERLFVLSNSSTLDLASINLQRGRDHGLPGYNEWREFCGLPRLETPADLSTAIASRSVADKILDLYKHPDNIDVWLGGLAENFLPRARTGPLFACLIGKQMKALRDGDWFWWENSHVFTDAQRRELEKHSLSRVICDNTGLTRVPMDAFQVGKFPEDFESCDSITGMNLEAWRETFPQDDKCGFPESVENGDFVHCEESGRRVLVYSCRHGYELQGREQLTCTQEGWDFQPPLCKDVNECADGAHPPCHASARCRNTKGGFQCLCADPYELGDDGRTCVDSGRLPRVTWISMSLAALLIGGFAGLTSTVICRWTRTGTKSTLPISETGGGTPELRCGKHQAVGTSPQRAAAQDSEQESAGMEGRDTHRLPRAL |
| Enzyme Length | 933 |
| Uniprot Accession Number | P07202 |
| Absorption | |
| Active Site | ACT_SITE 239; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Activity Regulation | |
| Binding Site | BINDING 238; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000250"; BINDING 399; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000250" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O; Xref=Rhea:RHEA:23336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:17606; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48956, Rhea:RHEA-COMP:12274, Rhea:RHEA-COMP:12275, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:46858, ChEBI:CHEBI:90870; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48960, Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:90870, ChEBI:CHEBI:90871; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O; Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12277, Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:90871, ChEBI:CHEBI:90872, ChEBI:CHEBI:90873; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; CATALYTIC ACTIVITY: Reaction=[thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3-iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine + [thyroglobulin]-dehydroalanine + 2 H2O; Xref=Rhea:RHEA:48968, Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12278, Rhea:RHEA-COMP:12279, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:90870, ChEBI:CHEBI:90871, ChEBI:CHEBI:90873, ChEBI:CHEBI:90874; EC=1.11.1.8; Evidence={ECO:0000250|UniProtKB:P09933}; |
| DNA Binding | |
| EC Number | 1.11.1.8 |
| Enzyme Function | FUNCTION: Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4). {ECO:0000250|UniProtKB:P09933}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis. |
| nucleotide Binding | |
| Features | Active site (1); Alternative sequence (5); Binding site (2); Chain (1); Compositional bias (1); Disulfide bond (8); Domain (2); Glycosylation (4); Metal binding (6); Natural variant (36); Region (1); Sequence conflict (14); Signal peptide (1); Site (1); Topological domain (2); Transmembrane (1) |
| Keywords | Alternative splicing;Calcium;Congenital hypothyroidism;Disease variant;Disulfide bond;EGF-like domain;Glycoprotein;Heme;Hydrogen peroxide;Iron;Membrane;Metal-binding;Oxidoreductase;Peroxidase;Reference proteome;Signal;Sushi;Thyroid hormones biosynthesis;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.; SUBCELLULAR LOCATION: [Isoform 3]: Cell surface. |
| Modified Residue | |
| Post Translational Modification | PTM: Glycosylated.; PTM: Heme is covalently bound through a H(2)O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface.; PTM: Cleaved in its N-terminal part. |
| Signal Peptide | SIGNAL 1..18; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 15613581; 1722671; 17468186; 19420105; 19730683; 67547; |
| Motif | |
| Gene Encoded By | |
| Mass | 102,963 |
| Kinetics | |
| Metal Binding | METAL 240; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 321; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 323; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 325; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 327; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 494; /note=Iron (heme b axial ligand); /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Rhea ID | RHEA:23336; RHEA:48956; RHEA:48960; RHEA:48964; RHEA:48968 |
| Cross Reference Brenda | 1.11.1.8;3.6.1.52; |