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Protein

Thyroid peroxidase

Gene

Tpo

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

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

Catalytic activityi

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

Cofactori

Protein has several cofactor binding sites:
  • Ca2+PROSITE-ProRule annotationNote: Binds 1 Ca2+ ion per heterodimer.PROSITE-ProRule annotation
  • heme bPROSITE-ProRule annotationNote: Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per heterodimer.PROSITE-ProRule annotation

Pathwayi: thyroid hormone biosynthesis

This protein is involved in the pathway thyroid hormone biosynthesis, which is part of Hormone biosynthesis.
View all proteins of this organism that are known to be involved in the pathway thyroid hormone biosynthesis and in Hormone biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei232Heme (covalent; via 2 links)By similarity1
Active sitei233Proton acceptorPROSITE-ProRule annotation1
Metal bindingi234CalciumPROSITE-ProRule annotation1
Metal bindingi313CalciumPROSITE-ProRule annotation1
Metal bindingi315Calcium; via carbonyl oxygenPROSITE-ProRule annotation1
Metal bindingi317CalciumPROSITE-ProRule annotation1
Metal bindingi319CalciumPROSITE-ProRule annotation1
Sitei384Transition state stabilizerPROSITE-ProRule annotation1
Binding sitei387Heme (covalent; via 2 links)By similarity1
Metal bindingi482Iron (heme axial ligand)PROSITE-ProRule annotation1

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • heme binding Source: InterPro
  • iodide peroxidase activity Source: RGD

GO - Biological processi

  • cellular response to nitric oxide Source: RGD
  • hormone biosynthetic process Source: UniProtKB-KW
  • hydrogen peroxide catabolic process Source: UniProtKB-KW
  • response to lipid Source: RGD
  • thyroid hormone generation Source: RGD

Keywordsi

Molecular functionOxidoreductase, Peroxidase
Biological processHydrogen peroxide, Thyroid hormones biosynthesis
LigandCalcium, Heme, Iron, Metal-binding

Enzyme and pathway databases

UniPathwayiUPA00194

Protein family/group databases

PeroxiBasei3973 RnoTPO

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroid peroxidase (EC:1.11.1.8By similarity)
Short name:
TPO
Gene namesi
Name:Tpo
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3900 Tpo

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 834ExtracellularSequence analysisAdd BLAST803
Transmembranei835 – 859HelicalSequence analysisAdd BLAST25
Topological domaini860 – 914CytoplasmicSequence analysisAdd BLAST55

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000002366532 – 914Thyroid peroxidaseAdd BLAST883

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi123N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi136 ↔ 152By similarity
Disulfide bondi253 ↔ 263By similarity
Disulfide bondi257 ↔ 278By similarity
Glycosylationi271N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi299N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi334N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi586 ↔ 643By similarity
Glycosylationi603N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi684 ↔ 709By similarity
Disulfide bondi730 ↔ 770By similarity
Disulfide bondi756 ↔ 782By similarity
Disulfide bondi788 ↔ 802By similarity
Disulfide bondi796 ↔ 811By similarity
Disulfide bondi813 ↔ 826By similarity

Post-translational modificationi

Heme is covalently bound through a H2O2-dependent autocatalytic process. Heme insertion is important for the delivery of protein at the cell surface (By similarity).By similarity
Cleaved in its N-terminal part.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP14650
PRIDEiP14650

Interactioni

Subunit structurei

Interacts with DUOX1, DUOX2 and CYBA.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006526

Structurei

3D structure databases

ProteinModelPortaliP14650
SMRiP14650
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini728 – 783SushiPROSITE-ProRule annotationAdd BLAST56
Domaini784 – 827EGF-like; calcium-bindingPROSITE-ProRule annotationAdd BLAST44

Sequence similaritiesi

Belongs to the peroxidase family. XPO subfamily.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG2408 Eukaryota
ENOG410XPZ3 LUCA
HOGENOMiHOG000016084
HOVERGENiHBG000071
InParanoidiP14650
PhylomeDBiP14650

Family and domain databases

CDDicd00033 CCP, 1 hit
Gene3Di1.10.640.10, 1 hit
InterProiView protein in InterPro
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR000152 EGF-type_Asp/Asn_hydroxyl_site
IPR018097 EGF_Ca-bd_CS
IPR010255 Haem_peroxidase
IPR019791 Haem_peroxidase_animal
IPR037120 Haem_peroxidase_sf
IPR035976 Sushi/SCR/CCP_sf
IPR000436 Sushi_SCR_CCP_dom
IPR029589 TPO
PANTHERiPTHR11475:SF60 PTHR11475:SF60, 1 hit
PfamiView protein in Pfam
PF03098 An_peroxidase, 1 hit
PF07645 EGF_CA, 1 hit
PF00084 Sushi, 1 hit
PRINTSiPR00457 ANPEROXIDASE
SMARTiView protein in SMART
SM00032 CCP, 1 hit
SM00181 EGF, 1 hit
SM00179 EGF_CA, 1 hit
SUPFAMiSSF48113 SSF48113, 1 hit
SSF57535 SSF57535, 1 hit
PROSITEiView protein in PROSITE
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

Sequencei

Sequence statusi: Complete.

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

P14650-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRTLGAMAVM LVVMGTAIFL PFLLRSRDIL GGKTMTSHVI SVVETSQLLV
60 70 80 90 100
DNAVYNTMKR NLKKRGVLSP AQLLSFSKLP ESTSGAISRA AEIMETSIQV
110 120 130 140 150
MKREQSQFST DALSADILAT IANLSGCLPF MLPPRCPDTC LANKYRPITG
160 170 180 190 200
VCNNRDHPRW GASNTALARW LPPVYEDGFS QPRGWNPNFL YHGFPLPPVR
210 220 230 240 250
EVTRHLIQVS NEAVTEDDQY SDFLPVWGQY IDHDIALTPQ STSTAAFWGG
260 270 280 290 300
VDCQLTCENQ NPCFPIQLPS NSSRTTACLP FYRSSAACGT GDQGALFGNL
310 320 330 340 350
SAANPRQQMN GLTSFLDAST VYGSSPGVEK QLRNWSSSAG LLRVNTLHLD
360 370 380 390 400
SGRAYLPFAS AACAPEPGAP HANRTPCFLA GDGRASEVPA LAAVHTLWLR
410 420 430 440 450
EHNRLATAFK AINTHWSANT AYQEARKVVG ALHQIITMRD YIPKILGPDA
460 470 480 490 500
FRQYVGPYEG YNPTVNPTVS NVFSTAAFRF GHATVHPLVR RLNTDFQDHT
510 520 530 540 550
ELPRLQLHDV FFRPWRLIQE GGLDPIVRGL LARPAKLQVQ EQLMNEELTE
560 570 580 590 600
RLFVLSNVGT LDLASLNLQR GRDHGLPGYN EWREFCGLSR LDTGAELNKA
610 620 630 640 650
IANRSMVNKI MELYKHADNI DVWLGGLAEK FLPGARTGPL FACIIGKQMK
660 670 680 690 700
ALRDGDRFWW ENSHVFTDAQ RQELEKHSLP RVICDNTGLT RVPVDAFRIG
710 720 730 740 750
KFPQDFESCE EIPSMDLRLW RETFPQDDKC VFPEKVDNGN FVHCEESGKL
760 770 780 790 800
VLVYSCFHGY KLQGQEQVTC TQNGWDSEPP VCKDVNECAD LTHPPCHSSA
810 820 830 840 850
KCKNTKGSFQ CVCTDPYMLG EDEKTCIDSG RLPRASWVSI ALGALLIGGL
860 870 880 890 900
ASLSWTVICR WTHADKKSTL LITERVTMES GFRKSQESGI SPQKAEVQDA
910
EQEPAYGSRV LLCE
Length:914
Mass (Da):101,460
Last modified:April 1, 1990 - v1
Checksum:iB700B89439E85191
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti194 – 195FP → LG in AAA42265 (PubMed:2691880).Curated2
Sequence conflicti198P → S in AAA42265 (PubMed:2691880).Curated1
Sequence conflicti228G → A in AAA42265 (PubMed:2691880).Curated1
Sequence conflicti592 – 594DTG → ETP in AAA42265 (PubMed:2691880).Curated3

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17396 mRNA Translation: CAA35257.1
M31655 mRNA Translation: AAA42265.1
PIRiS07047
UniGeneiRn.233736
Rn.91199

Genome annotation databases

UCSCiRGD:3900 rat

Similar proteinsi

Entry informationi

Entry nameiPERT_RAT
AccessioniPrimary (citable) accession number: P14650
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: May 23, 2018
This is version 162 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families
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