PERT_MOUSE
ID PERT_MOUSE Reviewed; 914 AA.
AC P35419; Q8C8B1;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Thyroid peroxidase;
DE Short=TPO;
DE EC=1.11.1.8 {ECO:0000250|UniProtKB:P09933};
DE Flags: Precursor;
GN Name=Tpo;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thyroid;
RX PubMed=7916704; DOI=10.1016/0378-1119(93)90141-o;
RA Kotani T., Umeki K., Yamamoto I., Takeuchi M., Takechi S., Nakayama T.,
RA Ohtaki S.;
RT "Nucleotide sequence of the cDNA encoding mouse thyroid peroxidase.";
RL Gene 123:289-290(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Head;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
CC -!- FUNCTION: Iodination and coupling of the hormonogenic tyrosines in
CC thyroglobulin to yield the thyroid hormones T(3) and T(4).
CC {ECO:0000250|UniProtKB:P09933}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + H2O2 + 2 iodide = diiodine + 2 H2O;
CC Xref=Rhea:RHEA:23336, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16382, ChEBI:CHEBI:17606; EC=1.11.1.8;
CC Evidence={ECO:0000250|UniProtKB:P09933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-L-tyrosine + H(+) + H2O2 + iodide =
CC [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48956,
CC Rhea:RHEA-COMP:12274, Rhea:RHEA-COMP:12275, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382,
CC ChEBI:CHEBI:46858, ChEBI:CHEBI:90870; EC=1.11.1.8;
CC Evidence={ECO:0000250|UniProtKB:P09933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-3-iodo-L-tyrosine + H(+) + H2O2 + iodide =
CC [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O; Xref=Rhea:RHEA:48960,
CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382,
CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871; EC=1.11.1.8;
CC Evidence={ECO:0000250|UniProtKB:P09933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 =
CC [thyroglobulin]-dehydroalanine + [thyroglobulin]-L-thyroxine + 2 H2O;
CC Xref=Rhea:RHEA:48964, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12277,
CC Rhea:RHEA-COMP:12278, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:90871, ChEBI:CHEBI:90872, ChEBI:CHEBI:90873; EC=1.11.1.8;
CC Evidence={ECO:0000250|UniProtKB:P09933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thyroglobulin]-3,5-diiodo-L-tyrosine + [thyroglobulin]-3-
CC iodo-L-tyrosine + H2O2 = [thyroglobulin]-3,3',5-triiodo-L-thyronine +
CC [thyroglobulin]-dehydroalanine + 2 H2O; Xref=Rhea:RHEA:48968,
CC Rhea:RHEA-COMP:12275, Rhea:RHEA-COMP:12276, Rhea:RHEA-COMP:12278,
CC Rhea:RHEA-COMP:12279, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:90870, ChEBI:CHEBI:90871, ChEBI:CHEBI:90873,
CC ChEBI:CHEBI:90874; EC=1.11.1.8;
CC Evidence={ECO:0000250|UniProtKB:P09933};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00298};
CC Note=Binds 1 Ca(2+) ion per heterodimer. {ECO:0000255|PROSITE-
CC ProRule:PRU00298};
CC -!- COFACTOR:
CC Name=heme b; Xref=ChEBI:CHEBI:60344;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00298};
CC Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per
CC heterodimer. {ECO:0000255|PROSITE-ProRule:PRU00298};
CC -!- PATHWAY: Hormone biosynthesis; thyroid hormone biosynthesis.
CC -!- SUBUNIT: Interacts with DUOX1, DUOX2 and CYBA. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}.
CC -!- PTM: Heme is covalently bound through a H(2)O(2)-dependent
CC autocatalytic process. Heme insertion is important for the delivery of
CC protein at the cell surface (By similarity). {ECO:0000250}.
CC -!- PTM: Cleaved in its N-terminal part. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
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DR EMBL; X60703; CAA43114.1; -; mRNA.
DR EMBL; AK047843; BAC33171.1; -; mRNA.
DR CCDS; CCDS25857.1; -.
DR PIR; JN0550; JN0550.
DR RefSeq; NP_033443.1; NM_009417.3.
DR AlphaFoldDB; P35419; -.
DR SMR; P35419; -.
DR STRING; 10090.ENSMUSP00000021005; -.
DR PeroxiBase; 3345; MmTPO.
DR GlyGen; P35419; 5 sites.
DR iPTMnet; P35419; -.
DR PhosphoSitePlus; P35419; -.
DR PaxDb; P35419; -.
DR PRIDE; P35419; -.
DR ProteomicsDB; 288126; -.
DR Antibodypedia; 2364; 596 antibodies from 35 providers.
DR DNASU; 22018; -.
DR Ensembl; ENSMUST00000021005; ENSMUSP00000021005; ENSMUSG00000020673.
DR GeneID; 22018; -.
DR KEGG; mmu:22018; -.
DR UCSC; uc007ngo.1; mouse.
DR CTD; 7173; -.
DR MGI; MGI:98813; Tpo.
DR VEuPathDB; HostDB:ENSMUSG00000020673; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000158104; -.
DR HOGENOM; CLU_006087_1_0_1; -.
DR InParanoid; P35419; -.
DR OMA; GPYEGYN; -.
DR OrthoDB; 276568at2759; -.
DR PhylomeDB; P35419; -.
DR TreeFam; TF314316; -.
DR Reactome; R-MMU-209968; Thyroxine biosynthesis.
DR UniPathway; UPA00194; -.
DR BioGRID-ORCS; 22018; 3 hits in 71 CRISPR screens.
DR ChiTaRS; Tpo; mouse.
DR PRO; PR:P35419; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P35419; protein.
DR Bgee; ENSMUSG00000020673; Expressed in trachea and 16 other tissues.
DR ExpressionAtlas; P35419; baseline and differential.
DR Genevisible; P35419; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0004447; F:iodide peroxidase activity; IEA:UniProtKB-EC.
DR GO; GO:0004601; F:peroxidase activity; IBA:GO_Central.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:MGI.
DR GO; GO:0042446; P:hormone biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR GO; GO:0006590; P:thyroid hormone generation; IEA:UniProtKB-UniPathway.
DR CDD; cd00033; CCP; 1.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR InterPro; IPR035976; Sushi/SCR/CCP_sf.
DR InterPro; IPR000436; Sushi_SCR_CCP_dom.
DR InterPro; IPR029589; TPO.
DR PANTHER; PTHR11475:SF60; PTHR11475:SF60; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF07645; EGF_CA; 1.
DR Pfam; PF00084; Sushi; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SMART; SM00032; CCP; 1.
DR SMART; SM00181; EGF; 1.
DR SMART; SM00179; EGF_CA; 1.
DR SUPFAM; SSF48113; SSF48113; 1.
DR SUPFAM; SSF57535; SSF57535; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS00435; PEROXIDASE_1; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
DR PROSITE; PS50923; SUSHI; 1.
PE 2: Evidence at transcript level;
KW Calcium; Disulfide bond; EGF-like domain; Glycoprotein; Heme;
KW Hydrogen peroxide; Iron; Membrane; Metal-binding; Oxidoreductase;
KW Peroxidase; Reference proteome; Signal; Sushi;
KW Thyroid hormones biosynthesis; Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..914
FT /note="Thyroid peroxidase"
FT /id="PRO_0000023663"
FT TOPO_DOM 32..834
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 835..859
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 860..914
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 728..783
FT /note="Sushi"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00302"
FT DOMAIN 784..827
FT /note="EGF-like; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 881..909
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 233
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 232
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000250"
FT BINDING 234
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 313
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 315
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 317
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 319
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 387
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000250"
FT BINDING 482
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT SITE 384
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT CARBOHYD 123
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 271
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 603
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 136..152
FT /evidence="ECO:0000250"
FT DISULFID 253..263
FT /evidence="ECO:0000250"
FT DISULFID 257..278
FT /evidence="ECO:0000250"
FT DISULFID 586..643
FT /evidence="ECO:0000250"
FT DISULFID 684..709
FT /evidence="ECO:0000250"
FT DISULFID 730..770
FT /evidence="ECO:0000250"
FT DISULFID 756..782
FT /evidence="ECO:0000250"
FT DISULFID 788..802
FT /evidence="ECO:0000250"
FT DISULFID 796..811
FT /evidence="ECO:0000250"
FT DISULFID 813..826
FT /evidence="ECO:0000250"
FT CONFLICT 614
FT /note="Y -> H (in Ref. 2; BAC33171)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 914 AA; 101342 MW; 595E9A0B71F3DD01 CRC64;
MRTLGAMAIM LVVMGTVIFL SFILRSRDIL CGKTMKSHVI SAVETSQLMV DHAVYNTMKR
NLKKREVLSP AQLLSFFKLP ESTSGAISRA AEIMETSIQV MKREQSQFST DALSADILGT
IANLSGCLPF MLPPRCPDTC LANKYRPITG ACNNRDHPRW GASNTALARW LPPVYEDGFS
QPKGWNPNFL YHGFPLPPVR EVTRHLIQVS NEAVTEDDQY SDFLPVWGQY IDHDIALTPQ
STSTAAFWGG VDCQLTCENQ NPCFPIQLPS NSSGTTACLP FYRSSAACGT GDQGALFGNL
SAANPRQQMN GLTSFLDAST VYGSSPGVEK QLRNWSSSAG LLRVNTLHLD AGRAYLPFAT
AACAPEPGTP RTNRTPCFLA GDGRASEVPA LAAVHTLWLR EHNRLASAFK AINKHWSANT
AYQEARKVVG ALHQIITMRD YIPKILGPDA FRQYVGPYEG YNPTVNPTVS NIFSTAAFRF
GHATVHPLVR RLNTDFQEHT ELPRLQLRDV FFRPWRLIQE GGLDPIVRGL LARAAKLQVQ
GQLMNEELTE RLFVLSNVGT LDLASLNLQR GRDHGLPDYN EWREFCGLSR LETPAELNKA
IANRSMVNKI MDLYKHADNI DVWLGGLAEK FLPGARTGPL FACIIGKQMK ALRDGDRFWW
ENTNVFTDAQ RQELEKHSLP RVICDNTGLT RVPVDAFRIG KFPQDFESCE DIPSMDLELW
RETFPQDDKC VFPEEVDNGN FVHCEESGKL VLVYSCFHGY KLQGQEQVTC TQKGWDSEPP
VCKDVNECAD LTHPPCHPSA QCKNTKGSFQ CVCTDPYVLG EDEKTCIDSG RLPRASWVSI
ALGALLIGGL ASLTWIVICR WTHADKKATL PITERVTTQS GCRKSQGRGI SPHKAAAQDT
GQEPASGSRV LLCE
