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P14650

- PERT_RAT

UniProt

P14650 - PERT_RAT

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Protein

Thyroid peroxidase

Gene

Tpo

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli

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

Protein has several cofactor binding sites:
  • Ca2+PROSITE-ProRule annotationNote: Binds 1 Ca(2+) 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei232 – 2321Heme (covalent; via 2 links)By similarity
Active sitei233 – 2331Proton acceptorPROSITE-ProRule annotation
Metal bindingi234 – 2341CalciumPROSITE-ProRule annotation
Metal bindingi313 – 3131CalciumPROSITE-ProRule annotation
Metal bindingi315 – 3151Calcium; via carbonyl oxygenPROSITE-ProRule annotation
Metal bindingi317 – 3171CalciumPROSITE-ProRule annotation
Metal bindingi319 – 3191CalciumPROSITE-ProRule annotation
Sitei384 – 3841Transition state stabilizerPROSITE-ProRule annotation
Binding sitei387 – 3871Heme (covalent; via 2 links)By similarity
Metal bindingi482 – 4821Iron (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: RGD

GO - Biological processi

  1. cellular response to nitric oxide Source: RGD
  2. hormone biosynthetic process Source: UniProtKB-KW
  3. hydrogen peroxide catabolic process Source: UniProtKB-KW
  4. response to lipid Source: RGD
  5. thyroid hormone generation Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Peroxidase

Keywords - Biological processi

Hydrogen peroxide, Thyroid hormones biosynthesis

Keywords - Ligandi

Calcium, Heme, Iron, Metal-binding

Enzyme and pathway databases

UniPathwayiUPA00194.

Protein family/group databases

PeroxiBasei3973. RnoTPO.

Names & Taxonomyi

Protein namesi
Recommended name:
Thyroid peroxidase (EC:1.11.1.8)
Short name:
TPO
Gene namesi
Name:Tpo
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi3900. Tpo.

Subcellular locationi

Membrane By similarity; Single-pass type I membrane protein By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 834803ExtracellularSequence AnalysisAdd
BLAST
Transmembranei835 – 85925HelicalSequence AnalysisAdd
BLAST
Topological domaini860 – 91455CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cell surface Source: RGD
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence AnalysisAdd
BLAST
Chaini32 – 914883Thyroid peroxidasePRO_0000023665Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi123 – 1231N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi136 ↔ 152By similarity
Disulfide bondi253 ↔ 263By similarity
Disulfide bondi257 ↔ 278By similarity
Glycosylationi271 – 2711N-linked (GlcNAc...)Sequence Analysis
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence Analysis
Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi586 ↔ 643By similarity
Glycosylationi603 – 6031N-linked (GlcNAc...)Sequence Analysis
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 H2O(2)-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.

Expressioni

Gene expression databases

GenevestigatoriP14650.

Interactioni

Subunit structurei

Interacts with DUOX1, DUOX2 and CYBA.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000006526.

Structurei

3D structure databases

ProteinModelPortaliP14650.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini728 – 78356SushiPROSITE-ProRule annotationAdd
BLAST
Domaini784 – 82744EGF-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.
HOGENOMiHOG000016084.
HOVERGENiHBG000071.
InParanoidiP14650.
PhylomeDBiP14650.

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.
PF00084. Sushi. 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]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti194 – 1952FP → LG in AAA42265. (PubMed:2691880)Curated
Sequence conflicti198 – 1981P → S in AAA42265. (PubMed:2691880)Curated
Sequence conflicti228 – 2281G → A in AAA42265. (PubMed:2691880)Curated
Sequence conflicti592 – 5943DTG → ETP in AAA42265. (PubMed:2691880)Curated

Sequence databases

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

Genome annotation databases

UCSCiRGD:3900. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X17396 mRNA. Translation: CAA35257.1 .
M31655 mRNA. Translation: AAA42265.1 .
PIRi S07047.
UniGenei Rn.233736.

3D structure databases

ProteinModelPortali P14650.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000006526.

Protein family/group databases

PeroxiBasei 3973. RnoTPO.

Proteomic databases

PaxDbi P14650.
PRIDEi P14650.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

UCSCi RGD:3900. rat.

Organism-specific databases

RGDi 3900. Tpo.

Phylogenomic databases

eggNOGi NOG262194.
HOGENOMi HOG000016084.
HOVERGENi HBG000071.
InParanoidi P14650.
PhylomeDBi P14650.

Enzyme and pathway databases

UniPathwayi UPA00194 .

Miscellaneous databases

NextBioi 610988.
PROi P14650.

Gene expression databases

Genevestigatori P14650.

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.
PF00084. Sushi. 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. "Complete nucleotide sequence of the cDNA for thyroid peroxidase in FRTL5 rat thyroid cells."
    Derwahl M., Seto P., Rapoport B.
    Nucleic Acids Res. 17:8380-8380(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Thyroid peroxidase: rat cDNA sequence, chromosomal localization in mouse, and regulation of gene expression by comparison to thyroglobulin in rat FRTL-5 cells."
    Isozaki O., Kohn L.D., Kozak C.A., Kimura S.
    Mol. Endocrinol. 3:1681-1692(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 145-914.

Entry informationi

Entry nameiPERT_RAT
AccessioniPrimary (citable) accession number: P14650
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: April 1, 1990
Last modified: November 26, 2014
This is version 145 of the entry and version 1 of the sequence. [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

External Data

Dasty 3