PXDN_MOUSE
ID PXDN_MOUSE Reviewed; 1475 AA.
AC Q3UQ28; A4FU83; E9QNQ9;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=Peroxidasin homolog {ECO:0000305};
DE EC=1.11.2.- {ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};
DE Contains:
DE RecName: Full=PXDN active fragment {ECO:0000250|UniProtKB:Q92626};
DE Flags: Precursor;
GN Name=Pxdn {ECO:0000312|MGI:MGI:1916925}; Synonyms=Kiaa0230;
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 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).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 370-1475.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=18929642; DOI=10.1016/j.freeradbiomed.2008.09.009;
RA Cheng G., Salerno J.C., Cao Z., Pagano P.J., Lambeth J.D.;
RT "Identification and characterization of VPO1, a new animal heme-containing
RT peroxidase.";
RL Free Radic. Biol. Med. 45:1682-1694(2008).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=19590037; DOI=10.2353/ajpath.2009.080693;
RA Peterfi Z., Donko A., Orient A., Sum A., Prokai A., Molnar B., Vereb Z.,
RA Rajnavolgyi E., Kovacs K.J., Muller V., Szabo A.J., Geiszt M.;
RT "Peroxidasin is secreted and incorporated into the extracellular matrix of
RT myofibroblasts and fibrotic kidney.";
RL Am. J. Pathol. 175:725-735(2009).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=18848646; DOI=10.1016/j.gep.2008.09.004;
RA Homma S., Shimada T., Hikake T., Yaginuma H.;
RT "Expression pattern of LRR and Ig domain-containing protein (LRRIG protein)
RT in the early mouse embryo.";
RL Gene Expr. Patterns 9:1-26(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=21907015; DOI=10.1016/j.ajhg.2011.08.005;
RA Khan K., Rudkin A., Parry D.A., Burdon K.P., McKibbin M., Logan C.V.,
RA Abdelhamed Z.I., Muecke J.S., Fernandez-Fuentes N., Laurie K.J., Shires M.,
RA Fogarty R., Carr I.M., Poulter J.A., Morgan J.E., Mohamed M.D., Jafri H.,
RA Raashid Y., Meng N., Piseth H., Toomes C., Casson R.J., Taylor G.R.,
RA Hammerton M., Sheridan E., Johnson C.A., Inglehearn C.F., Craig J.E.,
RA Ali M.;
RT "Homozygous mutations in PXDN cause congenital cataract, corneal opacity,
RT and developmental glaucoma.";
RL Am. J. Hum. Genet. 89:464-473(2011).
RN [9]
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=22842973; DOI=10.1038/nchembio.1038;
RA Bhave G., Cummings C.F., Vanacore R.M., Kumagai-Cresse C.,
RA Ero-Tolliver I.A., Rafi M., Kang J.S., Pedchenko V., Fessler L.I.,
RA Fessler J.H., Hudson B.G.;
RT "Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in
RT tissue genesis.";
RL Nat. Chem. Biol. 8:784-790(2012).
RN [10]
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 1272-CYS--PRO-1475.
RX PubMed=24895407; DOI=10.1093/hmg/ddu274;
RA Yan X., Sabrautzki S., Horsch M., Fuchs H., Gailus-Durner V., Beckers J.,
RA Hrabe de Angelis M., Graw J.;
RT "Peroxidasin is essential for eye development in the mouse.";
RL Hum. Mol. Genet. 23:5597-5614(2014).
RN [11]
RP FUNCTION.
RX PubMed=25708780; DOI=10.1016/j.freeradbiomed.2015.02.015;
RA Lazar E., Peterfi Z., Sirokmany G., Kovacs H.A., Klement E.,
RA Medzihradszky K.F., Geiszt M.;
RT "Structure-function analysis of peroxidasin provides insight into the
RT mechanism of collagen IV crosslinking.";
RL Free Radic. Biol. Med. 83:273-282(2015).
RN [12]
RP FUNCTION.
RX PubMed=28424209; DOI=10.1152/ajprenal.00096.2017;
RA Bhave G., Colon S., Ferrell N.;
RT "The Sulfilimine Cross-Link of Collagen IV Contributes to Kidney Tubular
RT Basement Membrane Stiffness.";
RL Am. J. Physiol. 313:F596-F602(2017).
RN [13]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29626421; DOI=10.1016/j.abb.2018.03.038;
RA Bathish B., Turner R., Paumann-Page M., Kettle A.J., Winterbourn C.C.;
RT "Characterisation of peroxidasin activity in isolated extracellular matrix
RT and direct detection of hypobromous acid formation.";
RL Arch. Biochem. Biophys. 646:120-127(2018).
RN [14]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=31817535; DOI=10.3390/ijms20246144;
RA Kim H.K., Ham K.A., Lee S.W., Choi H.S., Kim H.S., Kim H.K., Shin H.S.,
RA Seo K.Y., Cho Y., Nam K.T., Kim I.B., Joe Y.A.;
RT "Biallelic Deletion of Pxdn in Mice Leads to Anophthalmia and Severe Eye
RT Malformation.";
RL Int. J. Mol. Sci. 20:0-0(2019).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=32675287; DOI=10.1074/jbc.ra120.014504;
RA Bathish B., Paumann-Page M., Paton L.N., Kettle A.J., Winterbourn C.C.;
RT "Peroxidasin mediates bromination of tyrosine residues in the extracellular
RT matrix.";
RL J. Biol. Chem. 295:12697-12705(2020).
RN [16]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32571911; DOI=10.1073/pnas.2007749117;
RA He C., Song W., Weston T.A., Tran C., Kurtz I., Zuckerman J.E.,
RA Guagliardo P., Miner J.H., Ivanov S.V., Bougoure J., Hudson B.G., Colon S.,
RA Voziyan P.A., Bhave G., Fong L.G., Young S.G., Jiang H.;
RT "Peroxidasin-mediated bromine enrichment of basement membranes.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:15827-15836(2020).
RN [17]
RP PROTEOLYTIC CLEAVAGE.
RX PubMed=34679700; DOI=10.3390/antiox10101565;
RA Kovacs H.A., Lazar E., Varady G., Sirokmany G., Geiszt M.;
RT "Characterization of the Proprotein Convertase-Mediated Processing of
RT Peroxidasin and Peroxidasin-like Protein.";
RL Antioxidants 10:0-0(2021).
CC -!- FUNCTION: Catalyzes the two-electron oxidation of bromide by hydrogen
CC peroxide and generates hypobromite as a reactive intermediate which
CC mediates the formation of sulfilimine cross-links between methionine
CC and hydroxylysine residues within an uncross-linked collagen IV/COL4A1
CC NC1 hexamer (PubMed:31817535, PubMed:22842973, PubMed:29626421,
CC PubMed:25708780, PubMed:28424209). In turns, directly contributes to
CC the collagen IV network-dependent fibronectin/FN and laminin assembly,
CC which is required for full extracellular matrix (ECM)-mediated
CC signaling (By similarity). Thus, sulfilimine cross-links are essential
CC for growth factor-induced cell proliferation and survival in
CC endothelial cells, an event essential to basement membrane integrity
CC (By similarity). In addition, through the bromide oxidation, may
CC promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and
CC FAK pathways (By similarity). Moreover brominates alpha2 collagen IV
CC chain/COL4A2 at 'Tyr-1480' and leads to bromine enrichment of the
CC basement membranes (PubMed:32675287, PubMed:32571911). In vitro, can
CC also catalyze the two-electron oxidation of thiocyanate and iodide and
CC these two substrates could effectively compete with bromide and thus
CC inhibit the formation of sulfilimine bonds (By similarity). Binds
CC laminins (By similarity). May play a role in the organization of
CC eyeball structure and lens development during eye development
CC (PubMed:31817535, PubMed:24895407). {ECO:0000250|UniProtKB:Q92626,
CC ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:24895407,
CC ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:28424209,
CC ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535,
CC ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O2 + L-lysyl-[collagen] + L-methionyl-[collagen] =
CC [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + H(+) + 2 H2O;
CC Xref=Rhea:RHEA:66020, Rhea:RHEA-COMP:12751, Rhea:RHEA-COMP:16949,
CC Rhea:RHEA-COMP:16951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16044, ChEBI:CHEBI:16240, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:166867; Evidence={ECO:0000269|PubMed:22842973,
CC ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66021;
CC Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:28424209,
CC ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bromide + H2O2 = H2O + hypobromite; Xref=Rhea:RHEA:66016,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15858, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:29250; Evidence={ECO:0000269|PubMed:22842973,
CC ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:32571911,
CC ECO:0000269|PubMed:32675287, ECO:0000305|PubMed:28424209,
CC ECO:0000305|PubMed:31817535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66017;
CC Evidence={ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421,
CC ECO:0000269|PubMed:31817535, ECO:0000269|PubMed:32571911,
CC ECO:0000269|PubMed:32675287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=hypobromite + L-lysyl-[collagen] + L-methionyl-[collagen] =
CC [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + bromide + H(+) + H2O;
CC Xref=Rhea:RHEA:66024, Rhea:RHEA-COMP:12751, Rhea:RHEA-COMP:16949,
CC Rhea:RHEA-COMP:16951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15858, ChEBI:CHEBI:16044, ChEBI:CHEBI:29250,
CC ChEBI:CHEBI:29969, ChEBI:CHEBI:166867;
CC Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:29626421,
CC ECO:0000305|PubMed:28424209, ECO:0000305|PubMed:31817535};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66025;
CC Evidence={ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421,
CC ECO:0000269|PubMed:31817535, ECO:0000305|PubMed:22842973};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + hypobromite + L-methionyl-
CC [collagen] = [collagen]-(5R)-5-hydroxy-L-lysyl-N-S-L-methionyl-
CC [collagen] + bromide + H(+) + H2O; Xref=Rhea:RHEA:66012, Rhea:RHEA-
CC COMP:12752, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16950,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15858,
CC ChEBI:CHEBI:16044, ChEBI:CHEBI:29250, ChEBI:CHEBI:133442,
CC ChEBI:CHEBI:166866; Evidence={ECO:0000269|PubMed:22842973};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66013;
CC Evidence={ECO:0000305|PubMed:22842973};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + H2O2 + L-methionyl-
CC [collagen] = [collagen]-(5R)-5-hydroxy-L-lysyl-N-S-L-methionyl-
CC [collagen] + H(+) + 2 H2O; Xref=Rhea:RHEA:66008, Rhea:RHEA-
CC COMP:12752, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16950,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16044,
CC ChEBI:CHEBI:16240, ChEBI:CHEBI:133442, ChEBI:CHEBI:166866;
CC Evidence={ECO:0000269|PubMed:22842973};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=bromide + H(+) + H2O2 + L-tyrosyl-[protein] = 3-bromo-L-
CC tyrosyl-[protein] + 2 H2O; Xref=Rhea:RHEA:69360, Rhea:RHEA-
CC COMP:10136, Rhea:RHEA-COMP:17686, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:16240,
CC ChEBI:CHEBI:46858, ChEBI:CHEBI:183512;
CC Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69361;
CC Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hypobromite + L-tyrosyl-[protein] = 3-bromo-L-tyrosyl-
CC [protein] + H2O; Xref=Rhea:RHEA:69356, Rhea:RHEA-COMP:10136,
CC Rhea:RHEA-COMP:17686, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29250, ChEBI:CHEBI:46858, ChEBI:CHEBI:183512;
CC Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69357;
CC Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};
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 subunit. {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 subunit. {ECO:0000255|PROSITE-ProRule:PRU00298};
CC -!- ACTIVITY REGULATION: Thiocyanate inhibits the formation of 3-
CC bromotyrosine. {ECO:0000269|PubMed:32675287}.
CC -!- SUBUNIT: Homotrimer; disulfide-linked. The homotrimer form is
CC predominant. Homooligomer; disulfide-linked. Oligomerization occurs
CC intracellularly before C-terminal proteolytic cleavage (By similarity).
CC Interacts with PXDNL; this interaction inhibits the peroxidase activity
CC of PXDN (By similarity). {ECO:0000250|UniProtKB:Q92626}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:19590037}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q92626}. Cell surface
CC {ECO:0000250|UniProtKB:Q92626}. Secreted, extracellular space,
CC extracellular matrix, basement membrane {ECO:0000269|PubMed:22842973}.
CC Note=Adheres on the cell surface in 'hot spots'.
CC {ECO:0000250|UniProtKB:Q92626}.
CC -!- SUBCELLULAR LOCATION: [PXDN active fragment]: Secreted, extracellular
CC space, extracellular matrix {ECO:0000250|UniProtKB:Q92626}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the cardiovascular system. In
CC the embryo, expressed in the corneal epithelial layer. In the adult
CC eyes, expressed in the corneal and lens epithelium. Expressed in lung
CC (PubMed:31817535). {ECO:0000269|PubMed:18929642,
CC ECO:0000269|PubMed:21907015, ECO:0000269|PubMed:31817535}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all embryonic tissues at 10 dpc.
CC Detected at 7 dpc (PubMed:18848646, PubMed:18929642). At E11.5, faintly
CC expressed in the lens epithelium cells and in the anterior part of
CC primary fiber cells. At E13.5, strongly expressed in the developing
CC lens especially the lens epithelium cells and in the inner limiting
CC membrane. Additionally, it is also expressed in ocular mesenchymal
CC cells in the vitreous. At E17.5, expressed not only in the whole lens,
CC but also in the inner neuroblast layer. In the lens, appears to be
CC strongly expressed in the lens epithelial and at the posterior pole of
CC the lens (PubMed:18929642). {ECO:0000269|PubMed:18848646,
CC ECO:0000269|PubMed:18929642}.
CC -!- DOMAIN: The VWFC domain mediates the covalent links between monomers
CC throught disulfide bridges. Ig-like C2-type domains are required to
CC sulfilimine bond formation. The VWFC domain is not required for
CC trimerization. The LRR domain mediates high affinity binding to
CC laminin-1. {ECO:0000250|UniProtKB:Q92626}.
CC -!- PTM: Processed by FURIN and the proteolytic processing largely depends
CC on the peroxidase activity of PXDN (PubMed:34679700). The proteolytic
CC cleavage occurs after intracellular homotrimerization and releases into
CC the extracellular matrix a large, catalytically active fragment and a
CC smaller fragment consisting primarily of the C-terminal VWFC domain.
CC The processing enhances both peroxidase activity and sulfilimine cross-
CC links formation (By similarity). {ECO:0000250|UniProtKB:Q92626,
CC ECO:0000269|PubMed:34679700}.
CC -!- DISRUPTION PHENOTYPE: Homozygous mice for the PXDN gene show completely
CC or almost closed eyelids with small eyes, having no apparent external
CC morphological defects in other organs (PubMed:31817535). In addition,
CC mice show hair color change and the tail color is white and also have a
CC white spot at the ventral and dorsal region at a frequency of about
CC 94.1%. Some of mutants have severe cataracts in the eyes
CC (PubMed:31817535). {ECO:0000269|PubMed:31817535}.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
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DR EMBL; AK142872; BAE25216.1; -; mRNA.
DR EMBL; AC159626; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC165078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC112913; AAI12914.1; -; mRNA.
DR CCDS; CCDS25856.1; -.
DR RefSeq; NP_852060.2; NM_181395.2.
DR AlphaFoldDB; Q3UQ28; -.
DR SMR; Q3UQ28; -.
DR BioGRID; 213608; 4.
DR STRING; 10090.ENSMUSP00000113703; -.
DR GlyConnect; 2580; 2 N-Linked glycans (2 sites).
DR GlyGen; Q3UQ28; 7 sites, 2 N-linked glycans (2 sites).
DR iPTMnet; Q3UQ28; -.
DR PhosphoSitePlus; Q3UQ28; -.
DR MaxQB; Q3UQ28; -.
DR PaxDb; Q3UQ28; -.
DR PRIDE; Q3UQ28; -.
DR ProteomicsDB; 300361; -.
DR Antibodypedia; 2426; 63 antibodies from 14 providers.
DR Ensembl; ENSMUST00000122328; ENSMUSP00000113703; ENSMUSG00000020674.
DR GeneID; 69675; -.
DR KEGG; mmu:69675; -.
DR UCSC; uc007ngl.2; mouse.
DR CTD; 7837; -.
DR MGI; MGI:1916925; Pxdn.
DR VEuPathDB; HostDB:ENSMUSG00000020674; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000157666; -.
DR HOGENOM; CLU_006087_0_1_1; -.
DR InParanoid; Q3UQ28; -.
DR OMA; QHFKCAK; -.
DR OrthoDB; 276568at2759; -.
DR PhylomeDB; Q3UQ28; -.
DR TreeFam; TF314316; -.
DR Reactome; R-MMU-2243919; Crosslinking of collagen fibrils.
DR BioGRID-ORCS; 69675; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Pxdn; mouse.
DR PRO; PR:Q3UQ28; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q3UQ28; protein.
DR Bgee; ENSMUSG00000020674; Expressed in manus and 217 other tissues.
DR ExpressionAtlas; Q3UQ28; baseline and differential.
DR Genevisible; Q3UQ28; MM.
DR GO; GO:0005604; C:basement membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005201; F:extracellular matrix structural constituent; ISO:MGI.
DR GO; GO:0020037; F:heme binding; ISS:UniProtKB.
DR GO; GO:0043237; F:laminin-1 binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016684; F:oxidoreductase activity, acting on peroxide as acceptor; IDA:UniProtKB.
DR GO; GO:0004601; F:peroxidase activity; ISS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0070831; P:basement membrane assembly; IDA:UniProtKB.
DR GO; GO:0071711; P:basement membrane organization; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IMP:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; ISO:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:UniProtKB.
DR GO; GO:0001654; P:eye development; IMP:UniProtKB.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; ISS:UniProtKB.
DR GO; GO:0070207; P:protein homotrimerization; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR CDD; cd09826; peroxidasin_like; 1.
DR Gene3D; 1.10.640.10; -; 1.
DR Gene3D; 2.60.40.10; -; 4.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR019791; Haem_peroxidase_animal.
DR InterPro; IPR010255; Haem_peroxidase_sf.
DR InterPro; IPR037120; Haem_peroxidase_sf_animal.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013106; Ig_V-set.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR034824; Peroxidasin_peroxidase.
DR InterPro; IPR034828; Peroxidasin_vert.
DR InterPro; IPR001007; VWF_dom.
DR PANTHER; PTHR11475:SF75; PTHR11475:SF75; 3.
DR Pfam; PF03098; An_peroxidase; 1.
DR Pfam; PF07679; I-set; 4.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF00093; VWC; 1.
DR PRINTS; PR00457; ANPEROXIDASE.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 4.
DR SMART; SM00406; IGv; 3.
DR SMART; SM00369; LRR_TYP; 5.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00214; VWC; 1.
DR SUPFAM; SSF48113; SSF48113; 1.
DR SUPFAM; SSF48726; SSF48726; 4.
DR PROSITE; PS50835; IG_LIKE; 4.
DR PROSITE; PS51450; LRR; 5.
DR PROSITE; PS50292; PEROXIDASE_3; 1.
DR PROSITE; PS01208; VWFC_1; 1.
DR PROSITE; PS50184; VWFC_2; 1.
PE 1: Evidence at protein level;
KW Basement membrane; Calcium; Disulfide bond; Endoplasmic reticulum;
KW Extracellular matrix; Glycoprotein; Heme; Hydrogen peroxide;
KW Immunoglobulin domain; Iron; Leucine-rich repeat; Metal-binding;
KW Oxidoreductase; Peroxidase; Phosphoprotein; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1475
FT /note="Peroxidasin homolog"
FT /id="PRO_0000319620"
FT CHAIN 24..1333
FT /note="PXDN active fragment"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT /id="PRO_0000455176"
FT DOMAIN 24..60
FT /note="LRRNT"
FT REPEAT 58..81
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 82..105
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 107..129
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 130..153
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 154..177
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 179..201
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT DOMAIN 189..241
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT DOMAIN 243..329
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 339..425
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REPEAT 402..425
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT DOMAIN 430..517
FT /note="Ig-like C2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 518..607
FT /note="Ig-like C2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REPEAT 1148..1172
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 1267..1288
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT DOMAIN 1409..1467
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT REGION 1312..1407
FT /note="Required in homotrimerization"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT ACT_SITE 824
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 823
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 825
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 904
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 906
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 908
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 910
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 977
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 1071
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 974
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT SITE 1333
FT /note="Cleavage; by FURIN"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT MOD_RES 1173
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT MOD_RES 1177
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT CARBOHYD 716
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT CARBOHYD 728
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT CARBOHYD 961
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1277
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT CARBOHYD 1364
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250|UniProtKB:Q92626, ECO:0000255"
FT DISULFID 33..39
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 37..46
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 193..240
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 195..219
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 264..314
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 360..409
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 451..499
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 543..591
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 720..882
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 729..745
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 733
FT /note="Interchain (with C-1312); in homotrimer"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 844..854
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 848..872
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 956..967
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 1174..1231
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 1272..1298
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT DISULFID 1312
FT /note="Interchain (with C-733); in homotrimer"
FT /evidence="ECO:0000250|UniProtKB:Q92626"
FT MUTAGEN 1272..1475
FT /note="Missing: Kinky tail mutant mice show kinky tail and
FT white spot at the belly; additionally, homozygous mutants
FT show microphthalmia and anterior segment dysgenesis
FT including corneal opacity, severe iris bombe (forward-
FT bowing iris) and very shallow or absent anterior chamber."
FT /evidence="ECO:0000269|PubMed:24895407"
FT CONFLICT 549
FT /note="P -> Q (in Ref. 1; BAE25216)"
FT /evidence="ECO:0000305"
FT CONFLICT 1298
FT /note="C -> R (in Ref. 3; AAI12914)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1475 AA; 165103 MW; 7F49A5B0D4CDBEB6 CRC64;
MAVRPTRRCL LALLLCFAWW AMAVVASKQG AGCPSRCLCF RTTVRCMHLL LEAVPAVAPQ
TSILDLRFNR IREIQPGAFR RLRSLNTLLL NNNQIKKIPN GAFEDLENLK YLYLYKNEIQ
SIDRQAFKGL ASLEQLYLHF NQIETLDPES FQHLPKLERL FLHNNRITHL VPGTFSQLES
MKRLRLDSNA LHCDCEILWL ADLLKTYAQS GNAQAAATCE YPRRIQGRSV ATITPEELNC
ERPRITSEPQ DADVTSGNTV YFTCRAEGNP KPEIIWLRNN NELSMKTDSR LNLLDDGTLM
IQNTQEADEG VYQCMAKNVA GEAKTQEVTL RYLGSPARPT FVIQPQNTEV LVGESVTLEC
SATGHPLPQI TWTRGDRTPL PIDPRVNITP SGGLYIQNVA QSDSGEYTCF ASNSVDSIHA
TAFIIVQALP QFTVTPQSRV VIEGQTVDFQ CAAKGHPQPV IAWTKGGSQL SVDRRHLVLS
SGTLRISGVA LHDQGQYECQ AVNIIGSQKV VAHLTVQPRV TPVFASIPSD MTVEVGTNVQ
LPCSSQGEPE PAITWNKDGV QVTESGKFHI SPEGFLTIND VGTADAGRYE CVARNTIGYA
SVSMVLSVNV PDVSRNGDPY VATSIVEAIA TVDRAINSTR THLFDSRPRS PNDLLALFRY
PRDPYTVGQA RAGEIFERTL QLIQEHVQHG LMVDLNGTSY HYNDLVSPQY LSLIANLSGC
TAHRRVNNCS DMCFHQKYRT HDGTCNNLQH PMWGASLTAF ERLLKAVYEN GFNTPRGINS
QRQYNGHVLP MPRLVSTTLI GTEVITPDEQ FTHMLMQWGQ FLDHDLDSTV VALSQARFSD
GQHCSSVCSN DPPCFSVMIP PNDPRVRSGA RCMFFVRSSP VCGSGMTSLL MNSVYPREQI
NQLTSYIDAS NVYGSTDHEA RSIRDLASHR GLLRQGIVQR SGKPLLPFAT GPPTECMRDE
NESPIPCFLA GDHRANEQLG LTSMHTLWFR EHNRIAAELL KLNPHWDGDT VYHETRKIVG
AEIQHITYRH WLPKILGEVG MKMLGEYRGY DPSVNAGIFN AFATAAFRFG HTLINPLLYR
LDENFEPIPQ GHVPLHKAFF SPFRIVNEGG IDPLLRGLFG VAGKMRIPSQ LLNTELTERL
FSMAHTVALD LAAINIQRGR DHGIPPYHDY RVYCNLSAAY TFEDLKNEIK SPVIREKLQR
LYGSTLNIDL FPALMVEDLV PGSRLGPTLM CLLSTQFRRL RDGDRLWYEN PGVFSPAQLT
QLKQTSLARI LCDNSDNITR VQQDVFRVAE FPHGYSSCED IPRVDLRVWQ DCCEDCRTRG
QFNAFSYHFR GRRSLEFSYE DDKPTKRARW RKALSVKHGK HLSNATSATH EHLEGPATND
LKEFVLEMQK IITDLRKQIN SLESRLSTTE CVDDSGESHG GNTKWKKDPC TVCECKNGQI
TCFVEACQPA ACPQPVKVEG ACCPVCLKNT AEEKP
