PERL_MOUSE
ID PERL_MOUSE Reviewed; 710 AA.
AC Q5SW46;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Lactoperoxidase {ECO:0000303|PubMed:22343415};
DE Short=LPO {ECO:0000303|PubMed:22343415};
DE EC=1.11.1.7 {ECO:0000305|PubMed:34127712};
DE Flags: Precursor;
GN Name=Lpo {ECO:0000312|MGI:MGI:1923363};
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22343415; DOI=10.1016/j.freeradbiomed.2012.02.009;
RA Kim B.W., Esworthy R.S., Hahn M.A., Pfeifer G.P., Chu F.F.;
RT "Expression of lactoperoxidase in differentiated mouse colon epithelial
RT cells.";
RL Free Radic. Biol. Med. 52:1569-1576(2012).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=34127712; DOI=10.1038/s41598-021-91745-8;
RA Yamakaze J., Lu Z.;
RT "Deletion of the lactoperoxidase gene causes multisystem inflammation and
RT tumors in mice.";
RL Sci. Rep. 11:12429-12429(2021).
CC -!- FUNCTION: Heme-containing oxidoreductase which catalyzes the conversion
CC of thiocyanate (SCN(-)) into antimicrobial agent hypothiocyanous acid
CC (OSCN(-)) in the presence of hydrogen peroxide (H2O2) (By similarity).
CC Also involved in the conversion of iodide (I(-)) into hypoiodite
CC (IO(-)) in the presence of H2O2 (By similarity). Responsible for the
CC inactivation of a wide range of micro-organisms and hence, important
CC component of defense mechanism (By similarity). May be implicated in
CC airway host defense against infection (By similarity). May contribute
CC to maintaining an appropriate H2O2 cellular level, therefore protecting
CC cells from H2O2-caused injuries and inflammation (PubMed:34127712).
CC {ECO:0000250|UniProtKB:P22079, ECO:0000250|UniProtKB:P80025,
CC ECO:0000269|PubMed:34127712}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 a phenolic donor + H2O2 = 2 a phenolic radical donor + 2
CC H2O; Xref=Rhea:RHEA:56136, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:139520, ChEBI:CHEBI:139521; EC=1.11.1.7;
CC Evidence={ECO:0000305|PubMed:34127712};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56137;
CC Evidence={ECO:0000305|PubMed:34127712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + H2O2 + thiocyanate = H2O + hypothiocyanous acid;
CC Xref=Rhea:RHEA:69416, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:18022, ChEBI:CHEBI:133907;
CC Evidence={ECO:0000250|UniProtKB:P80025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69417;
CC Evidence={ECO:0000250|UniProtKB:P80025};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O2 + iodide = H2O + hypoiodite; Xref=Rhea:RHEA:69420,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16240, ChEBI:CHEBI:16382,
CC ChEBI:CHEBI:29232; Evidence={ECO:0000250|UniProtKB:P80025};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69421;
CC Evidence={ECO:0000250|UniProtKB:P80025};
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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P22079}.
CC Cytoplasm {ECO:0000269|PubMed:22343415}. Note=Expressed in the
CC cytoplasm in intestinal epithelial cells.
CC {ECO:0000269|PubMed:22343415}.
CC -!- TISSUE SPECIFICITY: Expressed in the colon, including colonocytes and
CC mucin-containing goblet cells (PubMed:22343415, PubMed:34127712). Not
CC detected in the ileum (PubMed:22343415). {ECO:0000269|PubMed:22343415,
CC ECO:0000269|PubMed:34127712}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice exhibit inflammation and lesions in
CC the cardiovascular, respiratory, digestive or excretory systems,
CC neuropathology, and tumors, with high incidence.
CC {ECO:0000269|PubMed:34127712}.
CC -!- MISCELLANEOUS: Thiocyanate (SCN(-)) and hypothiocyanite (OSCN(-)) are
CC bound in the distal heme cavity. The iodide ion (I(-)) occupies a
CC position which is stabilized by the interactions with heme moiety, His-
CC 224, Arg-370 and Glu-373. Hydrogen peroxide is held between the heme
CC iron and His-224. {ECO:0000250|UniProtKB:P80025}.
CC -!- SIMILARITY: Belongs to the peroxidase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00298}.
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DR RefSeq; NP_536345.2; NM_080420.2.
DR RefSeq; XP_011247600.1; XM_011249298.2.
DR SMR; Q5SW46; -.
DR STRING; 10090.ENSMUSP00000099466; -.
DR PeroxiBase; 3343; MmLPO.
DR iPTMnet; Q5SW46; -.
DR PhosphoSitePlus; Q5SW46; -.
DR MaxQB; Q5SW46; -.
DR PaxDb; Q5SW46; -.
DR PRIDE; Q5SW46; -.
DR ProteomicsDB; 359909; -.
DR Antibodypedia; 18358; 277 antibodies from 32 providers.
DR DNASU; 76113; -.
DR Ensembl; ENSMUST00000103177.10; ENSMUSP00000099466.4; ENSMUSG00000009356.13.
DR GeneID; 76113; -.
DR KEGG; mmu:76113; -.
DR UCSC; uc007kus.2; mouse.
DR CTD; 4025; -.
DR MGI; MGI:1923363; Lpo.
DR VEuPathDB; HostDB:ENSMUSG00000009356; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000160488; -.
DR HOGENOM; CLU_006087_1_1_1; -.
DR InParanoid; Q5SW46; -.
DR OMA; PHGFVDC; -.
DR OrthoDB; 276568at2759; -.
DR PhylomeDB; Q5SW46; -.
DR TreeFam; TF314316; -.
DR Reactome; R-MMU-8941413; Events associated with phagocytolytic activity of PMN cells.
DR BioGRID-ORCS; 76113; 0 hits in 64 CRISPR screens.
DR ChiTaRS; Lpo; mouse.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q5SW46; protein.
DR Bgee; ENSMUSG00000009356; Expressed in parotid gland and 50 other tissues.
DR ExpressionAtlas; Q5SW46; baseline and differential.
DR Genevisible; Q5SW46; MM.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0004601; F:peroxidase activity; IDA:MGI.
DR GO; GO:0036393; F:thiocyanate peroxidase activity; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR GO; GO:0001580; P:detection of chemical stimulus involved in sensory perception of bitter taste; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 1.10.640.10; -; 1.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR InterPro; IPR029587; LPO.
DR PANTHER; PTHR11475:SF67; PTHR11475:SF67; 1.
DR Pfam; PF03098; An_peroxidase; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SUPFAM; SSF48113; SSF48113; 1.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
PE 1: Evidence at protein level;
KW Antimicrobial; Calcium; Cytoplasm; Disulfide bond; Heme; Iron;
KW Metal-binding; Nitration; Oxidoreductase; Peroxidase; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..80
FT /evidence="ECO:0000250|UniProtKB:P22079"
FT /id="PRO_0000456225"
FT CHAIN 81..710
FT /note="Lactoperoxidase"
FT /evidence="ECO:0000250|UniProtKB:P22079"
FT /id="PRO_0000456226"
FT ACT_SITE 224
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 223
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 225
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 299
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 301
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 303
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 305
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 373
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 466
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 370
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT MOD_RES 313
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:A5JUY8"
FT MOD_RES 480
FT /note="3'-nitrotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P11678"
FT DISULFID 130..143
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 244..254
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 248..272
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 352..363
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 571..628
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT DISULFID 669..694
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
SQ SEQUENCE 710 AA; 80124 MW; 53D49184910601AE CRC64;
MKVLLHLPAL LASLTLLQTA ASASDDPTAE TDIIHDTVEE VKVWVNKAFL DSRDRLKMAM
TTKIHSTRHL SDYLKHAKGR TRTAIRSGQV WEESLKKLSQ FLTNVTGQGL DLTLLSWEAG
CDPPAPTMTC NISSPYRTIT GYCNNRKNPA LGSANRALAR WLPAEYEDGL SLPYGWTPGK
MRNGFPLPQP REVSNQIAAY LNEEDVLDQK RSMLFMQWGQ IVDHDMDFAP ETEMGSDTYT
KAQCDEHCIQ GDNCFPIMFP PGDPKLKTQG KCMPFFRAGF VCPTPPYKSL AREQINALTS
FLDASLVYSP EPSLANRLRN LSSPLGLMAV NEEVSDNGRP FPPFVKMKPS PCEVINATAG
VPCFLAGDSR ASEQILLATS HTLFIREHNR LATELSRLNP HWDRETLYQE ARKIMGAFIQ
ITTFRDYLPI LLGDEMQKWI PPYQGYNESV DPRISNVFTF ALRFGHLEIP STVYRLDENY
QPWGSESELP LHTVFFNTWR LVKDGGIDPL VRGLLAKNAK LMHQNKMMTG ELRNKLFQPN
HTIHGFDLAS INIQRSRDHG QPGYNSWRAF CGLSQPKTLE ELSAVMKNEV LAKKLMDLYG
TPSNIDIWLG AVAEPLVHRG RVGPLLTCLL GQQFQRIRDG DRFWWENPGV FTEKQRESLQ
KMSFSRLVCD NTGIDKVPLN PFQANAYPHG FVDCSSIDKL DLSPWASVKE
