Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P07202

- PERT_HUMAN

UniProt

P07202 - PERT_HUMAN

Protein

Thyroid peroxidase

Gene

TPO

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 190 (01 Oct 2014)
      Sequence version 4 (13 Nov 2007)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T3 and T4.

    Catalytic activityi

    2 iodide + H2O2 + 2 H+ = 2 iodine + 2 H2O.
    [Thyroglobulin]-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O.
    [Thyroglobulin]-3-iodo-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O.
    2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-L-thyroxine + [thyroglobulin]-aminoacrylate + 2 H2O.
    [Thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + 2 H2O.

    Cofactori

    Binds 1 calcium ion per heterodimer.PROSITE-ProRule annotation
    Binds 1 heme B (iron-protoporphyrin IX) group covalently per heterodimer.PROSITE-ProRule annotation

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei238 – 2381Heme (covalent; via 2 links)By similarity
    Active sitei239 – 2391Proton acceptorPROSITE-ProRule annotation
    Metal bindingi240 – 2401CalciumPROSITE-ProRule annotation
    Metal bindingi321 – 3211CalciumPROSITE-ProRule annotation
    Metal bindingi323 – 3231Calcium; via carbonyl oxygenPROSITE-ProRule annotation
    Metal bindingi325 – 3251CalciumPROSITE-ProRule annotation
    Metal bindingi327 – 3271CalciumPROSITE-ProRule annotation
    Sitei396 – 3961Transition state stabilizerPROSITE-ProRule annotation
    Binding sitei399 – 3991Heme (covalent; via 2 links)By similarity
    Metal bindingi494 – 4941Iron (heme axial ligand)PROSITE-ProRule annotation

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. heme binding Source: InterPro
    3. iodide peroxidase activity Source: UniProtKB-EC
    4. peroxidase activity Source: ProtInc

    GO - Biological processi

    1. cellular nitrogen compound metabolic process Source: Reactome
    2. embryonic hemopoiesis Source: DFLAT
    3. hormone biosynthetic process Source: UniProtKB-KW
    4. hydrogen peroxide catabolic process Source: UniProtKB-KW
    5. small molecule metabolic process Source: Reactome
    6. thyroid hormone generation Source: Reactome

    Keywords - Molecular functioni

    Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Hydrogen peroxide, Thyroid hormones biosynthesis

    Keywords - Ligandi

    Calcium, Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_15292. Thyroxine biosynthesis.
    UniPathwayiUPA00194.

    Protein family/group databases

    PeroxiBasei3318. HsTPO01.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Thyroid peroxidase (EC:1.11.1.8)
    Short name:
    TPO
    Gene namesi
    Name:TPO
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:12015. TPO.

    Subcellular locationi

    GO - Cellular componenti

    1. cell surface Source: UniProtKB-SubCell
    2. extracellular space Source: UniProt
    3. integral component of plasma membrane Source: ProtInc
    4. mitochondrion Source: Ensembl
    5. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    An alternative splicing in the thyroperoxidase mRNA can cause Graves' disease.
    Thyroid dyshormonogenesis 2A (TDH2A) [MIM:274500]: A disorder due to defective conversion of accumulated iodide to organically bound iodine. The iodide organification defect can be partial or complete.16 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti53 – 531A → P in TDH2A. 1 Publication
    VAR_021622
    Natural varianti240 – 2401D → N in TDH2A; loss of activity. 1 Publication
    VAR_021623
    Natural varianti307 – 3071N → T in TDH2A. 1 Publication
    VAR_021624
    Natural varianti326 – 3261A → T in TDH2A. 1 Publication
    VAR_021625
    Natural varianti378 – 3781E → K in TDH2A. 1 Publication
    VAR_025784
    Natural varianti433 – 4331V → M in TDH2A. 1 Publication
    VAR_021626
    Natural varianti447 – 4471I → F in TDH2A. 2 Publications
    VAR_015375
    Natural varianti453 – 4531Y → D in TDH2A. 3 Publications
    VAR_006060
    Natural varianti458 – 4581L → P in TDH2A. 1 Publication
    VAR_021627
    Natural varianti491 – 4911R → H in TDH2A. 1 Publication
    Corresponds to variant rs201165648 [ dbSNP | Ensembl ].
    VAR_021628
    Natural varianti493 – 4931G → S in TDH2A. 1 Publication
    VAR_021629
    Natural varianti499 – 4991P → L in TDH2A. 1 Publication
    VAR_021630
    Natural varianti527 – 5271W → C in TDH2A. 1 Publication
    VAR_021631
    Natural varianti533 – 5331G → C in TDH2A; partial defect; expression slightly lower in efficiency and more degenerative than wild-type enzyme. 1 Publication
    VAR_027229
    Natural varianti574 – 5752Missing in TDH2A; partial defect; expressed on the plasma membrane surface at less than half the rate of wild-type enzyme.
    VAR_027230
    Natural varianti590 – 5901G → S in TDH2A. 1 Publication
    VAR_027231
    Natural varianti648 – 6481R → Q in TDH2A. 1 Publication
    VAR_013138
    Natural varianti660 – 6601Q → E in TDH2A. 1 Publication
    Corresponds to variant rs121908088 [ dbSNP | Ensembl ].
    VAR_021632
    Natural varianti665 – 6651R → W in TDH2A; fails to localize to the plasma membrane. 1 Publication
    VAR_021633
    Natural varianti693 – 6931R → W in TDH2A. 2 Publications
    VAR_021634
    Natural varianti771 – 7711G → R in TDH2A; fails to localize to the plasma membrane. 1 Publication
    VAR_021635
    Natural varianti796 – 7961D → Y in TDH2A. 1 Publication
    VAR_021636
    Natural varianti799 – 7991E → K in TDH2A. 3 Publications
    Corresponds to variant rs121908085 [ dbSNP | Ensembl ].
    VAR_006062
    Natural varianti808 – 8081C → R in TDH2A. 1 Publication
    VAR_021637
    Natural varianti839 – 8391V → I in TDH2A. 1 Publication
    VAR_027235

    Keywords - Diseasei

    Congenital hypothyroidism, Disease mutation

    Organism-specific databases

    MIMi274500. phenotype.
    Orphaneti95716. Familial thyroid dyshormonogenesis.
    PharmGKBiPA36694.

    Protein family/group databases

    Allergomei9554. Hom s TPO.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 933915Thyroid peroxidasePRO_0000023662Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi129 – 1291N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi142 ↔ 158By similarity
    Disulfide bondi259 ↔ 269By similarity
    Disulfide bondi263 ↔ 286By similarity
    Glycosylationi307 – 3071N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi342 – 3421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi569 – 5691N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi598 ↔ 655By similarity
    Disulfide bondi696 ↔ 721By similarity
    Disulfide bondi800 ↔ 814By similarity
    Disulfide bondi808 ↔ 823By similarity
    Disulfide bondi825 ↔ 838By similarity

    Post-translational modificationi

    Glycosylated.
    Heme is covalently bound through a H2O(2)-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface.
    Cleaved in its N-terminal part.

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PaxDbiP07202.
    PRIDEiP07202.

    PTM databases

    PhosphoSiteiP07202.

    Expressioni

    Gene expression databases

    ArrayExpressiP07202.
    BgeeiP07202.
    GenevestigatoriP07202.

    Organism-specific databases

    HPAiCAB009587.
    HPA007987.

    Interactioni

    Subunit structurei

    Interacts with DUOX1, DUOX2 and CYBA.1 Publication

    Structurei

    3D structure databases

    ProteinModelPortaliP07202.
    SMRiP07202. Positions 149-732.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 846828ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini872 – 93362CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei847 – 87125HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini740 – 79556SushiPROSITE-ProRule annotationAdd
    BLAST
    Domaini796 – 83944EGF-like; calcium-bindingPROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peroxidase family. XPO subfamily.PROSITE-ProRule annotation
    Contains 1 EGF-like domain.PROSITE-ProRule annotation
    Contains 1 Sushi (CCP/SCR) domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Signal, Sushi, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG262194.
    HOVERGENiHBG000071.
    InParanoidiP07202.
    KOiK00431.
    OMAiIMETSIQ.
    OrthoDBiEOG7D2FD6.
    PhylomeDBiP07202.
    TreeFamiTF314316.

    Family and domain databases

    Gene3Di1.10.640.10. 2 hits.
    InterProiIPR000742. EG-like_dom.
    IPR001881. EGF-like_Ca-bd_dom.
    IPR013032. EGF-like_CS.
    IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
    IPR018097. EGF_Ca-bd_CS.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    IPR000436. Sushi_SCR_CCP.
    IPR029589. TPO.
    [Graphical view]
    PANTHERiPTHR11475:SF60. PTHR11475:SF60. 1 hit.
    PfamiPF03098. An_peroxidase. 1 hit.
    PF07645. EGF_CA. 1 hit.
    [Graphical view]
    PRINTSiPR00457. ANPEROXIDASE.
    SMARTiSM00032. CCP. 1 hit.
    SM00179. EGF_CA. 1 hit.
    [Graphical view]
    SUPFAMiSSF48113. SSF48113. 1 hit.
    SSF57535. SSF57535. 1 hit.
    PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00435. PEROXIDASE_1. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    PS50923. SUSHI. 1 hit.
    [Graphical view]

    Sequences (8)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 8 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P07202-1) [UniParc]FASTAAdd to Basket

    Also known as: TPO1

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MRALAVLSVT LVMACTEAFF PFISRGKELL WGKPEESRVS SVLEESKRLV    50
    DTAMYATMQR NLKKRGILSP AQLLSFSKLP EPTSGVIARA AEIMETSIQA 100
    MKRKVNLKTQ QSQHPTDALS EDLLSIIANM SGCLPYMLPP KCPNTCLANK 150
    YRPITGACNN RDHPRWGASN TALARWLPPV YEDGFSQPRG WNPGFLYNGF 200
    PLPPVREVTR HVIQVSNEVV TDDDRYSDLL MAWGQYIDHD IAFTPQSTSK 250
    AAFGGGADCQ MTCENQNPCF PIQLPEEARP AAGTACLPFY RSSAACGTGD 300
    QGALFGNLST ANPRQQMNGL TSFLDASTVY GSSPALERQL RNWTSAEGLL 350
    RVHARLRDSG RAYLPFVPPR APAACAPEPG IPGETRGPCF LAGDGRASEV 400
    PSLTALHTLW LREHNRLAAA LKALNAHWSA DAVYQEARKV VGALHQIITL 450
    RDYIPRILGP EAFQQYVGPY EGYDSTANPT VSNVFSTAAF RFGHATIHPL 500
    VRRLDASFQE HPDLPGLWLH QAFFSPWTLL RGGGLDPLIR GLLARPAKLQ 550
    VQDQLMNEEL TERLFVLSNS STLDLASINL QRGRDHGLPG YNEWREFCGL 600
    PRLETPADLS TAIASRSVAD KILDLYKHPD NIDVWLGGLA ENFLPRARTG 650
    PLFACLIGKQ MKALRDGDWF WWENSHVFTD AQRRELEKHS LSRVICDNTG 700
    LTRVPMDAFQ VGKFPEDFES CDSITGMNLE AWRETFPQDD KCGFPESVEN 750
    GDFVHCEESG RRVLVYSCRH GYELQGREQL TCTQEGWDFQ PPLCKDVNEC 800
    ADGAHPPCHA SARCRNTKGG FQCLCADPYE LGDDGRTCVD SGRLPRVTWI 850
    SMSLAALLIG GFAGLTSTVI CRWTRTGTKS TLPISETGGG TPELRCGKHQ 900
    AVGTSPQRAA AQDSEQESAG MEGRDTHRLP RAL 933
    Length:933
    Mass (Da):102,963
    Last modified:November 13, 2007 - v4
    Checksum:iF67C5F1A4AEE0B29
    GO
    Isoform 2 (identifier: P07202-2) [UniParc]FASTAAdd to Basket

    Also known as: TPO2

    The sequence of this isoform differs from the canonical sequence as follows:
         534-590: Missing.

    Note: Lacks exon 10. Found in normal thyroid tissues as well as Graves'tissues. Rapidly degraded after synthesis, does not reach the cell surface. Inactive.

    Show »
    Length:876
    Mass (Da):96,699
    Checksum:iF4CF0D050608F808
    GO
    Isoform 3 (identifier: P07202-3) [UniParc]FASTAAdd to Basket

    Also known as: TPO3, Graves' disease, TPOzaninelli

    The sequence of this isoform differs from the canonical sequence as follows:
         874-933: TRTGTKSTLP...RDTHRLPRAL → RVLGWKAGIL...SAGRLFSQHG

    Note: Lacks exon 16. Found in normal thyroid tissues as well as Graves'tissues. Active.

    Show »
    Length:929
    Mass (Da):102,771
    Checksum:i423AC29EEB27277B
    GO
    Isoform 4 (identifier: P07202-4) [UniParc]FASTAAdd to Basket

    Also known as: TPO4

    The sequence of this isoform differs from the canonical sequence as follows:
         796-839: Missing.

    Note: Lacks exon 14. Active.

    Show »
    Length:889
    Mass (Da):98,327
    Checksum:iF9C575FC93A450C8
    GO
    Isoform 5 (identifier: P07202-5) [UniParc]FASTAAdd to Basket

    Also known as: TPO5

    The sequence of this isoform differs from the canonical sequence as follows:
         274-446: Missing.

    Note: Lacks exon 8. Does not fold correctly. Does not reach the cell surface.

    Show »
    Length:760
    Mass (Da):84,581
    Checksum:i3C6150EA7E602B78
    GO
    Isoform 6 (identifier: P07202-6) [UniParc]FASTAAdd to Basket

    Also known as: TPO6

    The sequence of this isoform differs from the canonical sequence as follows:
         534-590: Missing.
         669-933: Missing.

    Note: Lacks exons 10, 12, 13, 14 and 16.

    Show »
    Length:611
    Mass (Da):67,293
    Checksum:i7AD0B6FA3206066A
    GO
    Isoform 2-3 (identifier: P07202-7) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         534-590: Missing.
         874-933: TRTGTKSTLP...RDTHRLPRAL → RVLGWKAGIL...SAGRLFSQHG

    Note: Lacks exons 10 and 16.

    Show »
    Length:872
    Mass (Da):96,507
    Checksum:i3EDC31BFE86C24E2
    GO
    Isoform 2-4 (identifier: P07202-8) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         534-590: Missing.
         796-839: Missing.

    Note: Lacks exons 10 and 14.

    Show »
    Length:832
    Mass (Da):92,063
    Checksum:i7C6D17A3B62C1D7D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti70 – 701P → G in AAA61217. 1 PublicationCurated
    Sequence conflicti354 – 3541A → G1 PublicationCurated
    Sequence conflicti354 – 3541A → G(PubMed:3654979)Curated
    Sequence conflicti371 – 3711A → R in AAA61215. (PubMed:3475693)Curated
    Sequence conflicti371 – 3711A → R in AAA61216. (PubMed:3475693)Curated
    Sequence conflicti381 – 3811I → N1 PublicationCurated
    Sequence conflicti381 – 3811I → N(PubMed:3654979)Curated
    Sequence conflicti574 – 5741D → N in CAA68467. (PubMed:3453124)Curated
    Sequence conflicti732 – 7321W → C in AAN11302. (PubMed:12454013)Curated
    Sequence conflicti748 – 7481V → M(PubMed:3453124)Curated
    Sequence conflicti748 – 7481V → M(PubMed:12454013)Curated
    Sequence conflicti816 – 8161N → S in AAL74416. 1 PublicationCurated
    Sequence conflicti872 – 8721R → K(PubMed:3453124)Curated
    Sequence conflicti872 – 8721R → K(PubMed:12454013)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti53 – 531A → P in TDH2A. 1 Publication
    VAR_021622
    Natural varianti240 – 2401D → N in TDH2A; loss of activity. 1 Publication
    VAR_021623
    Natural varianti257 – 2571A → S.3 Publications
    Corresponds to variant rs4927611 [ dbSNP | Ensembl ].
    VAR_006057
    Natural varianti307 – 3071N → T in TDH2A. 1 Publication
    VAR_021624
    Natural varianti326 – 3261A → T in TDH2A. 1 Publication
    VAR_021625
    Natural varianti373 – 3731A → S.1 Publication
    Corresponds to variant rs2280132 [ dbSNP | Ensembl ].
    VAR_006058
    Natural varianti378 – 3781E → K in TDH2A. 1 Publication
    VAR_025784
    Natural varianti398 – 3981S → T.1 Publication
    Corresponds to variant rs2175977 [ dbSNP | Ensembl ].
    VAR_006059
    Natural varianti433 – 4331V → M in TDH2A. 1 Publication
    VAR_021626
    Natural varianti447 – 4471I → F in TDH2A. 2 Publications
    VAR_015375
    Natural varianti453 – 4531Y → D in TDH2A. 3 Publications
    VAR_006060
    Natural varianti458 – 4581L → P in TDH2A. 1 Publication
    VAR_021627
    Natural varianti491 – 4911R → H in TDH2A. 1 Publication
    Corresponds to variant rs201165648 [ dbSNP | Ensembl ].
    VAR_021628
    Natural varianti493 – 4931G → S in TDH2A. 1 Publication
    VAR_021629
    Natural varianti499 – 4991P → L in TDH2A. 1 Publication
    VAR_021630
    Natural varianti527 – 5271W → C in TDH2A. 1 Publication
    VAR_021631
    Natural varianti533 – 5331G → C in TDH2A; partial defect; expression slightly lower in efficiency and more degenerative than wild-type enzyme. 1 Publication
    VAR_027229
    Natural varianti574 – 5752Missing in TDH2A; partial defect; expressed on the plasma membrane surface at less than half the rate of wild-type enzyme.
    VAR_027230
    Natural varianti590 – 5901G → S in TDH2A. 1 Publication
    VAR_027231
    Natural varianti618 – 6181V → M.
    Corresponds to variant rs10189135 [ dbSNP | Ensembl ].
    VAR_027232
    Natural varianti648 – 6481R → Q in TDH2A. 1 Publication
    VAR_013138
    Natural varianti660 – 6601Q → E in TDH2A. 1 Publication
    Corresponds to variant rs121908088 [ dbSNP | Ensembl ].
    VAR_021632
    Natural varianti665 – 6651R → W in TDH2A; fails to localize to the plasma membrane. 1 Publication
    VAR_021633
    Natural varianti693 – 6931R → W in TDH2A. 2 Publications
    VAR_021634
    Natural varianti706 – 7061M → V.
    Corresponds to variant rs13431173 [ dbSNP | Ensembl ].
    VAR_027233
    Natural varianti725 – 7251T → P.5 Publications
    Corresponds to variant rs732609 [ dbSNP | Ensembl ].
    VAR_006061
    Natural varianti771 – 7711G → R in TDH2A; fails to localize to the plasma membrane. 1 Publication
    VAR_021635
    Natural varianti793 – 7931L → P.
    Corresponds to variant rs28991293 [ dbSNP | Ensembl ].
    VAR_027234
    Natural varianti796 – 7961D → Y in TDH2A. 1 Publication
    VAR_021636
    Natural varianti799 – 7991E → K in TDH2A. 3 Publications
    Corresponds to variant rs121908085 [ dbSNP | Ensembl ].
    VAR_006062
    Natural varianti808 – 8081C → R in TDH2A. 1 Publication
    VAR_021637
    Natural varianti839 – 8391V → I in TDH2A. 1 Publication
    VAR_027235
    Natural varianti846 – 8461R → W.
    Corresponds to variant rs28913014 [ dbSNP | Ensembl ].
    VAR_027236
    Natural varianti847 – 8471V → A.4 Publications
    Corresponds to variant rs1126799 [ dbSNP | Ensembl ].
    VAR_027237

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei274 – 446173Missing in isoform 5. 1 PublicationVSP_007268Add
    BLAST
    Alternative sequencei534 – 59057Missing in isoform 2, isoform 2-3, isoform 2-4 and isoform 6. 2 PublicationsVSP_004665Add
    BLAST
    Alternative sequencei669 – 933265Missing in isoform 6. CuratedVSP_007270Add
    BLAST
    Alternative sequencei796 – 83944Missing in isoform 4 and isoform 2-4. CuratedVSP_007269Add
    BLAST
    Alternative sequencei874 – 93360TRTGT…LPRAL → RVLGWKAGILTGCREPSEGK VAGHCRTASCSQNHRTTLFQ TQANRKSAGRLFSQHG in isoform 3 and isoform 2-3. 1 PublicationVSP_004666Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02969 mRNA. Translation: AAA61215.1.
    J02970 mRNA. Translation: AAA61216.1.
    Y00406 mRNA. Translation: CAA68467.1.
    M25715
    , M25702, M25703, M25704, M25705, M25706, M25707, M25708, M25709, M25710, M25711, M25712, M25713, M25714 Genomic DNA. Translation: AAA97517.1.
    X17358 mRNA. Translation: CAA35235.1.
    M17755 mRNA. Translation: AAA61217.2.
    AF439430 mRNA. Translation: AAL74416.1.
    AF533528 mRNA. Translation: AAN04471.1.
    AY136822 mRNA. Translation: AAN11302.1.
    AF533529 mRNA. Translation: AAN04472.1.
    AF533530 mRNA. Translation: AAN04473.1.
    AF533531 mRNA. Translation: AAN04474.1.
    M55702 mRNA. Translation: AAA61219.1.
    M55702 mRNA. Translation: AAA61218.1.
    CCDSiCCDS1643.1. [P07202-1]
    CCDS1644.1. [P07202-2]
    CCDS1646.1. [P07202-5]
    PIRiA32413. OPHUIT.
    RefSeqiNP_000538.3. NM_000547.5. [P07202-1]
    NP_001193673.1. NM_001206744.1. [P07202-1]
    NP_001193674.1. NM_001206745.1. [P07202-2]
    NP_783650.1. NM_175719.3. [P07202-2]
    NP_783652.1. NM_175721.3. [P07202-4]
    NP_783653.1. NM_175722.3. [P07202-5]
    UniGeneiHs.467554.

    Genome annotation databases

    EnsembliENST00000329066; ENSP00000329869; ENSG00000115705. [P07202-1]
    ENST00000345913; ENSP00000318820; ENSG00000115705. [P07202-1]
    ENST00000346956; ENSP00000263886; ENSG00000115705. [P07202-4]
    ENST00000382198; ENSP00000371633; ENSG00000115705. [P07202-5]
    ENST00000382201; ENSP00000371636; ENSG00000115705. [P07202-2]
    GeneIDi7173.
    KEGGihsa:7173.
    UCSCiuc002qwr.3. human. [P07202-1]
    uc002qwu.3. human. [P07202-2]
    uc010yio.2. human. [P07202-5]
    uc010yip.2. human. [P07202-4]

    Polymorphism databases

    DMDMi160281455.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Thyroid peroxidase entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J02969 mRNA. Translation: AAA61215.1 .
    J02970 mRNA. Translation: AAA61216.1 .
    Y00406 mRNA. Translation: CAA68467.1 .
    M25715
    , M25702 , M25703 , M25704 , M25705 , M25706 , M25707 , M25708 , M25709 , M25710 , M25711 , M25712 , M25713 , M25714 Genomic DNA. Translation: AAA97517.1 .
    X17358 mRNA. Translation: CAA35235.1 .
    M17755 mRNA. Translation: AAA61217.2 .
    AF439430 mRNA. Translation: AAL74416.1 .
    AF533528 mRNA. Translation: AAN04471.1 .
    AY136822 mRNA. Translation: AAN11302.1 .
    AF533529 mRNA. Translation: AAN04472.1 .
    AF533530 mRNA. Translation: AAN04473.1 .
    AF533531 mRNA. Translation: AAN04474.1 .
    M55702 mRNA. Translation: AAA61219.1 .
    M55702 mRNA. Translation: AAA61218.1 .
    CCDSi CCDS1643.1. [P07202-1 ]
    CCDS1644.1. [P07202-2 ]
    CCDS1646.1. [P07202-5 ]
    PIRi A32413. OPHUIT.
    RefSeqi NP_000538.3. NM_000547.5. [P07202-1 ]
    NP_001193673.1. NM_001206744.1. [P07202-1 ]
    NP_001193674.1. NM_001206745.1. [P07202-2 ]
    NP_783650.1. NM_175719.3. [P07202-2 ]
    NP_783652.1. NM_175721.3. [P07202-4 ]
    NP_783653.1. NM_175722.3. [P07202-5 ]
    UniGenei Hs.467554.

    3D structure databases

    ProteinModelPortali P07202.
    SMRi P07202. Positions 149-732.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P07202.
    ChEMBLi CHEMBL1839.
    DrugBanki DB00389. Carbimazole.
    DB00763. Methimazole.
    DB00550. Propylthiouracil.
    GuidetoPHARMACOLOGYi 2526.

    Protein family/group databases

    Allergomei 9554. Hom s TPO.
    PeroxiBasei 3318. HsTPO01.

    PTM databases

    PhosphoSitei P07202.

    Polymorphism databases

    DMDMi 160281455.

    Proteomic databases

    PaxDbi P07202.
    PRIDEi P07202.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000329066 ; ENSP00000329869 ; ENSG00000115705 . [P07202-1 ]
    ENST00000345913 ; ENSP00000318820 ; ENSG00000115705 . [P07202-1 ]
    ENST00000346956 ; ENSP00000263886 ; ENSG00000115705 . [P07202-4 ]
    ENST00000382198 ; ENSP00000371633 ; ENSG00000115705 . [P07202-5 ]
    ENST00000382201 ; ENSP00000371636 ; ENSG00000115705 . [P07202-2 ]
    GeneIDi 7173.
    KEGGi hsa:7173.
    UCSCi uc002qwr.3. human. [P07202-1 ]
    uc002qwu.3. human. [P07202-2 ]
    uc010yio.2. human. [P07202-5 ]
    uc010yip.2. human. [P07202-4 ]

    Organism-specific databases

    CTDi 7173.
    GeneCardsi GC02P001396.
    H-InvDB HIX0029848.
    HGNCi HGNC:12015. TPO.
    HPAi CAB009587.
    HPA007987.
    MIMi 274500. phenotype.
    606765. gene.
    neXtProti NX_P07202.
    Orphaneti 95716. Familial thyroid dyshormonogenesis.
    PharmGKBi PA36694.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG262194.
    HOVERGENi HBG000071.
    InParanoidi P07202.
    KOi K00431.
    OMAi IMETSIQ.
    OrthoDBi EOG7D2FD6.
    PhylomeDBi P07202.
    TreeFami TF314316.

    Enzyme and pathway databases

    UniPathwayi UPA00194 .
    Reactomei REACT_15292. Thyroxine biosynthesis.

    Miscellaneous databases

    ChiTaRSi TPO. human.
    GenomeRNAii 7173.
    NextBioi 28112.
    PROi P07202.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P07202.
    Bgeei P07202.
    Genevestigatori P07202.

    Family and domain databases

    Gene3Di 1.10.640.10. 2 hits.
    InterProi IPR000742. EG-like_dom.
    IPR001881. EGF-like_Ca-bd_dom.
    IPR013032. EGF-like_CS.
    IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
    IPR018097. EGF_Ca-bd_CS.
    IPR010255. Haem_peroxidase.
    IPR019791. Haem_peroxidase_animal.
    IPR000436. Sushi_SCR_CCP.
    IPR029589. TPO.
    [Graphical view ]
    PANTHERi PTHR11475:SF60. PTHR11475:SF60. 1 hit.
    Pfami PF03098. An_peroxidase. 1 hit.
    PF07645. EGF_CA. 1 hit.
    [Graphical view ]
    PRINTSi PR00457. ANPEROXIDASE.
    SMARTi SM00032. CCP. 1 hit.
    SM00179. EGF_CA. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48113. SSF48113. 1 hit.
    SSF57535. SSF57535. 1 hit.
    PROSITEi PS00010. ASX_HYDROXYL. 1 hit.
    PS01186. EGF_2. 1 hit.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00435. PEROXIDASE_1. 1 hit.
    PS50292. PEROXIDASE_3. 1 hit.
    PS50923. SUSHI. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Human thyroid peroxidase: complete cDNA and protein sequence, chromosome mapping, and identification of two alternately spliced mRNAs."
      Kimura S., Kotani T., McBride O.W., Umeki K., Hirai K., Nakayama T., Ohtaki S.
      Proc. Natl. Acad. Sci. U.S.A. 84:5555-5559(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS PRO-725 AND ALA-847.
    2. "Complete nucleotide sequence of the human thyroperoxidase-microsomal antigen cDNA."
      Libert F., Ruel J., Ludgate M., Swillens S., Alexander N., Vassart G., Dinsart C.
      Nucleic Acids Res. 15:6735-6735(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS PRO-725 AND ALA-847.
      Tissue: Thyroid.
    3. "Structure of the human thyroid peroxidase gene: comparison and relationship to the human myeloperoxidase gene."
      Kimura S., Hong Y.S., Kotani T., Ohtaki S., Kikkawa F.
      Biochemistry 28:4481-4489(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    4. "Nucleotide sequence of the alternatively spliced human thyroid peroxidase cDNA, TPO-2."
      Barnett P.S., Banga J.P., Watkins J., Huang G.C., Gluckman D.R.B., Page M.J., McGregor A.M.
      Nucleic Acids Res. 18:670-670(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Thyroid.
    5. Rapoport B.
      Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-257.
      Tissue: Thyroid.
    6. "Homo sapiens thyroid peroxidase (TPO) variant mRNA, alternatively spliced sequence."
      Hennen G.P., Igout A., Melen L.B.
      Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), VARIANTS SER-257; PRO-725 AND ALA-847.
      Tissue: Thyroid.
    7. "Increasing diversity of human thyroperoxidase generated by alternative splicing. Characterization by molecular cloning of new transcripts with single- and multispliced mRNAs."
      Ferrand M., Le Fourn V., Franc J.-L.
      J. Biol. Chem. 278:3793-3800(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4; 5; 6; 2-3 AND 2-4), VARIANTS PRO-725 AND ALA-847.
      Tissue: Thyroid.
    8. "Isolation of a complementary DNA clone for thyroid microsomal antigen. Homology with the gene for thyroid peroxidase."
      Seto P., Hirayu H., Magnusson R.P., Gestautas J., Portmann L., Degroot L.J., Rapoport B.
      J. Clin. Invest. 80:1205-1208(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 217-496.
    9. "Evidence for an alternate splicing in the thyroperoxidase messenger from patients with Graves' disease."
      Zanelli E., Henry M., Charvet B., Malthiery Y.
      Biochem. Biophys. Res. Commun. 170:735-741(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 670-933 (ISOFORM 3), ALTERNATIVE SPLICING IN GRAVES' DISEASE.
      Tissue: Thyroid.
    10. "Identification of a novel partner of duox: EFP1, a thioredoxin-related protein."
      Wang D., De Deken X., Milenkovic M., Song Y., Pirson I., Dumont J.E., Miot F.
      J. Biol. Chem. 280:3096-3103(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DUOX1; DUOX2 AND CYBA.
    11. "Identification of five novel inactivating mutations in the human thyroid peroxidase gene by denaturing gradient gel electrophoresis."
      Bikker H., Vulsma T., Baas F., de Vijlder J.J.M.
      Hum. Mutat. 6:9-16(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A ASP-453; SER-590 AND LYS-799, VARIANTS SER-257; SER-373; THR-398 AND PRO-725.
    12. "Molecular analysis of mutated thyroid peroxidase detected in patients with total iodide organification defects."
      Bikker H., Baas F., De Vijlder J.J.M.
      J. Clin. Endocrinol. Metab. 82:649-653(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A PHE-447.
    13. "A novel mutation in the TPO gene in goitrous hypothyroid patients with iodide organification defect."
      Santos C.L.S., Bikker H., Rego K.G.M., Nascimento A.C., Tambascia M., De Vijlder J.J.M., Medeiros-Neto G.
      Clin. Endocrinol. (Oxf.) 51:165-172(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A GLU-660.
    14. "Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping."
      Pannain S., Weiss R.E., Jackson C.E., Dian D., Beck J.C., Sheffield V.C., Cox N., Refetoff S.
      J. Clin. Endocrinol. Metab. 84:1061-1071(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A GLN-648 AND LYS-799.
    15. "A novel mutation in the human thyroid peroxidase gene resulting in a total iodide organification defect."
      Kotani T., Umeki K., Yamamoto I., Maesaka H., Tachibana K., Ohtaki S.
      J. Endocrinol. 160:267-273(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A ASN-240, CHARACTERIZATION OF VARIANT TDH2A ASN-240.
    16. "Two decades of screening for congenital hypothyroidism in The Netherlands: TPO gene mutations in total iodide organification defects (an update)."
      Bakker B., Bikker H., Vulsma T., de Randamie J.S.E., Wiedijk B.M., De Vijlder J.J.M.
      J. Clin. Endocrinol. Metab. 85:3708-3712(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A THR-326; PHE-447; ASP-453; CYS-527; TRP-693 AND LYS-799.
    17. "Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism."
      Ambrugger P., Stoeva I., Biebermann H., Torresani T., Leitner C., Grueters A.
      Eur. J. Endocrinol. 145:19-24(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A PRO-458 AND HIS-491.
    18. "Two novel missense mutations in the thyroid peroxidase gene, R665W and G771R, result in a localization defect and cause congenital hypothyroidism."
      Umeki K., Kotani T., Kawano J., Suganuma T., Yamamoto I., Aratake Y., Furujo M., Ichiba Y.
      Eur. J. Endocrinol. 146:491-498(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A TRP-665 AND ARG-771, CHARACTERIZATION OF VARIANTS TDH2A TRP-665 AND ARG-771.
    19. "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."
      Niu D.-M., Hwang B., Chu Y.-K., Liao C.-J., Wang P.-L., Lin C.-Y.
      J. Clin. Endocrinol. Metab. 87:4208-4212(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A PRO-53.
    20. "Mutation analysis of thyroid peroxidase gene in Chinese patients with total iodide organification defect: identification of five novel mutations."
      Wu J.-Y., Shu S.-G., Yang C.-F., Lee C.-C., Tsai F.-J.
      J. Endocrinol. 172:627-635(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A SER-493 AND TYR-796.
    21. "Genetics of specific phenotypes of congenital hypothyroidism: a population-based approach."
      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.
      Thyroid 12:945-951(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A ILE-839.
    22. "Partial iodide organification defect caused by a novel mutation of the thyroid peroxidase gene in three siblings."
      Kotani T., Umeki K., Kawano J., Suganuma T., Hishinuma A., Ieiri T., Harada S.
      Clin. Endocrinol. (Oxf.) 59:198-206(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A CYS-533 AND ASP-574-575-LEU DEL, CHARACTERIZATION OF VARIANTS TDH2A CYS-533 AND ASP-574-575-LEU DEL.
    23. "Five novel inactivating mutations in the thyroid peroxidase gene responsible for congenital goiter and iodide organification defect."
      Rivolta C.M., Esperante S.A., Gruneiro-Papendieck L., Chiesa A., Moya C.M., Domene S., Varela V., Targovnik H.M.
      Hum. Mutat. 22:259-259(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS TDH2A THR-307; MET-433; LEU-499 AND ARG-808.
    24. "Monoallelic expression of mutant thyroid peroxidase allele causing total iodide organification defect."
      Fugazzola L., Cerutti N., Mannavola D., Vannucchi G., Fallini C., Persani L., Beck-Peccoz P.
      J. Clin. Endocrinol. Metab. 88:3264-3271(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A TRP-693.
    25. "Two novel mutations in the thyroid peroxidase gene with goitrous hypothyroidism."
      Tajima T., Tsubaki J., Fujieda K.
      Endocr. J. 52:643-645(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A LYS-378.
    26. "Goitrous congenital hypothyroidism and hearing impairment associated with mutations in the TPO and SLC26A4/PDS genes."
      Pfarr N., Borck G., Turk A., Napiontek U., Keilmann A., Mueller-Forell W., Kopp P., Pohlenz J.
      J. Clin. Endocrinol. Metab. 91:2678-2681(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT TDH2A ASP-453.

    Entry informationi

    Entry nameiPERT_HUMAN
    AccessioniPrimary (citable) accession number: P07202
    Secondary accession number(s): P09934
    , P09935, Q8IUL0, Q8NF94, Q8NF95, Q8NF96, Q8NF97, Q8TCI9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: November 13, 2007
    Last modified: October 1, 2014
    This is version 190 of the entry and version 4 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3