PXDN_HUMAN
ID PXDN_HUMAN Reviewed; 1479 AA.
AC Q92626; A8QM65; D6W4Y0; Q4KMG2;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Peroxidasin homolog {ECO:0000305};
DE EC=1.11.2.- {ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:27697841, ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:29982533, ECO:0000269|PubMed:32571911};
DE AltName: Full=Melanoma-associated antigen MG50;
DE AltName: Full=Peroxidasin 1 {ECO:0000303|PubMed:25713063};
DE Short=hsPxd01 {ECO:0000303|PubMed:25713063};
DE AltName: Full=Vascular peroxidase 1;
DE AltName: Full=p53-responsive gene 2 protein;
DE Contains:
DE RecName: Full=PXDN active fragment {ECO:0000305|PubMed:27697841};
DE Flags: Precursor;
GN Name=PXDN {ECO:0000312|HGNC:HGNC:14966};
GN Synonyms=KIAA0230, MG50, PRG2, PXD01, VPO, VPO1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=10441517; DOI=10.1006/bbrc.1999.1123;
RA Horikoshi N., Cong J., Kley N., Shenk T.;
RT "Isolation of differentially expressed cDNAs from p53-dependent apoptotic
RT cells: activation of the human homologue of the Drosophila peroxidasin
RT gene.";
RL Biochem. Biophys. Res. Commun. 261:864-869(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=11103812;
RA Mitchell M.S., Kan-Mitchell J., Minev B., Edman C., Deans R.J.;
RT "A novel melanoma gene (MG50) encoding the interleukin 1 receptor
RT antagonist and six epitopes recognized by human cytolytic T lymphocytes.";
RL Cancer Res. 60:6448-6456(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 3D-STRUCTURE MODELING, FUNCTION,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, HEME COFACTOR, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-1479 (ISOFORM 2).
RC TISSUE=Chondrosarcoma;
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 [7]
RP PROTEIN SEQUENCE OF 1337-1357, PROTEOLYTIC CLEAVAGE, SITE, MUTAGENESIS OF
RP 1335-ARG-ARG-1336, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27697841; DOI=10.1074/jbc.m116.745935;
RA Colon S., Bhave G.;
RT "Proprotein Convertase Processing Enhances Peroxidasin Activity to
RT Reinforce Collagen IV.";
RL J. Biol. Chem. 291:24009-24016(2016).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1176 AND SER-1180, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18318008; DOI=10.1002/pmic.200700884;
RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D.,
RA Zou H., Gu J.;
RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment
RT and fractionation of phosphopeptides with strong anion exchange
RT chromatography.";
RL Proteomics 8:1346-1361(2008).
RN [9]
RP SUBCELLULAR LOCATION.
RA Cheng G.;
RL Unpublished observations (FEB-2008).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP INDUCTION BY TGFB1.
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 [11]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-1178.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [12]
RP CATALYTIC ACTIVITY, FUNCTION, AND SUBUNIT.
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 [13]
RP INTERACTION WITH PXDNL.
RX PubMed=24253521; DOI=10.1093/cvr/cvt256;
RA Peterfi Z., Toth Z.E., Kovacs H.A., Lazar E., Sum A., Donko A.,
RA Sirokmany G., Shah A.M., Geiszt M.;
RT "Peroxidasin-like protein: a novel peroxidase homologue in the human
RT heart.";
RL Cardiovasc. Res. 101:393-399(2014).
RN [14]
RP SUBUNIT, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-736; GLN-823;
RP ASP-826; CYS-1315; CYS-1316 AND CYS-1319, AND DISULFIDE BOND.
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 [15]
RP SUBUNIT, GLYCOSYLATION AT ASN-640; ASN-699; ASN-719; ASN-731; ASN-865;
RP ASN-1178; ASN-1280; ASN-1368 AND ASN-1425, DOMAIN, IDENTIFICATION BY MASS
RP SPECTROMETRY, DISULFIDE BOND, FUNCTION, CATALYTIC ACTIVITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=25713063; DOI=10.1074/jbc.m114.632273;
RA Soudi M., Paumann-Page M., Delporte C., Pirker K.F., Bellei M.,
RA Edenhofer E., Stadlmayr G., Battistuzzi G., Boudjeltia K.Z.,
RA Furtmueller P.G., Van Antwerpen P., Obinger C.;
RT "Multidomain human peroxidasin 1 is a highly glycosylated and stable
RT homotrimeric high spin ferric peroxidase.";
RL J. Biol. Chem. 290:10876-10890(2015).
RN [16]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=26178375; DOI=10.1074/jbc.m115.673996;
RA Ero-Tolliver I.A., Hudson B.G., Bhave G.;
RT "The Ancient Immunoglobulin Domains of Peroxidasin Are Required to Form
RT Sulfilimine Cross-links in Collagen IV.";
RL J. Biol. Chem. 290:21741-21748(2015).
RN [17]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=28154175; DOI=10.1074/jbc.m117.775213;
RA Paumann-Page M., Katz R.S., Bellei M., Schwartz I., Edenhofer E.,
RA Sevcnikar B., Soudi M., Hofbauer S., Battistuzzi G., Furtmueller P.G.,
RA Obinger C.;
RT "Pre-steady-state Kinetics Reveal the Substrate Specificity and Mechanism
RT of Halide Oxidation of Truncated Human Peroxidasin 1.";
RL J. Biol. Chem. 292:4583-4592(2017).
RN [18]
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF GLN-823.
RX PubMed=29982533; DOI=10.1093/cvr/cvy179;
RA Medfai H., Khalil A., Rousseau A., Nuyens V., Paumann-Page M.,
RA Sevcnikar B., Furtmueller P.G., Obinger C., Moguilevsky N., Peulen O.,
RA Herfs M., Castronovo V., Amri M., Van Antwerpen P., Vanhamme L.,
RA Zouaoui Boudjeltia K.;
RT "Human peroxidasin 1 promotes angiogenesis through ERK1/2, Akt, and FAK
RT pathways.";
RL Cardiovasc. Res. 115:463-475(2019).
RN [19]
RP ACTIVITY REGULATION.
RX PubMed=31953133; DOI=10.1016/j.abb.2020.108267;
RA Sevcnikar B., Paumann-Page M., Hofbauer S., Pfanzagl V., Furtmueller P.G.,
RA Obinger C.;
RT "Reaction of human peroxidasin 1 compound I and compound II with one-
RT electron donors.";
RL Arch. Biochem. Biophys. 681:108267-108267(2020).
RN [20]
RP FUNCTION, AND DOMAIN.
RX PubMed=32485152; DOI=10.1016/j.abb.2020.108443;
RA Sevcnikar B., Schaffner I., Chuang C.Y., Gamon L., Paumann-Page M.,
RA Hofbauer S., Davies M.J., Furtmueller P.G., Obinger C.;
RT "The leucine-rich repeat domain of human peroxidasin 1 promotes binding to
RT laminin in basement membranes.";
RL Arch. Biochem. Biophys. 689:108443-108443(2020).
RN [21]
RP SUBUNIT, REGION, DOMAIN, AND DISULFIDE BOND.
RX PubMed=31295557; DOI=10.1016/j.bbapap.2019.07.002;
RA Paumann-Page M., Tscheliessnig R., Sevcnikar B., Katz R.S., Schwartz I.,
RA Hofbauer S., Pfanzagl V., Furtmueller P.G., Obinger C.;
RT "Monomeric and homotrimeric solution structures of truncated human
RT peroxidasin 1 variants.";
RL Biochim. Biophys. Acta 1868:140249-140249(2020).
RN [22]
RP FUNCTION, AND SUBUNIT.
RX PubMed=32543734; DOI=10.1096/fj.201902899r;
RA Lee S.W., Kim H.K., Naidansuren P., Ham K.A., Choi H.S., Ahn H.Y., Kim M.,
RA Kang D.H., Kang S.W., Joe Y.A.;
RT "Peroxidasin is essential for endothelial cell survival and growth
RT signaling by sulfilimine crosslink-dependent matrix assembly.";
RL FASEB J. 34:10228-10241(2020).
RN [23]
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 [24]
RP PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF CYS-736; GLN-823; ASP-826; CYS-1315;
RP 1335-ARG-ARG-1336 AND 1354-ARG-LYS-1355, FUNCTION, SITE, AND SUBCELLULAR
RP LOCATION.
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).
RN [25]
RP INVOLVEMENT IN ASGD7, AND VARIANT ASGD7 CYS-880.
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).
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:18929642, PubMed:22842973, PubMed:27697841,
CC PubMed:28154175, PubMed:19590037, PubMed:25708780, PubMed:25713063,
CC PubMed:34679700). In turns, directly contributes to the collagen IV
CC network-dependent fibronectin/FN and laminin assembly, which is
CC required for full extracellular matrix (ECM)-mediated signaling
CC (PubMed:32543734, PubMed:34679700, PubMed:19590037). Thus, sulfilimine
CC cross-links are essential for growth factor-induced cell proliferation
CC and survival in endothelial cells, an event essential to basement
CC membrane integrity (PubMed:32543734). In addition, through the bromide
CC oxidation, may promote tubulogenesis and induce angiogenesis through
CC ERK1/2, Akt, and FAK pathways (PubMed:25713063). Moreover brominates
CC alpha2 collagen IV chain/COL4A2 at 'Tyr-1485' and leads to bromine
CC enrichment of the basement membranes (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 (PubMed:28154175). Binds
CC laminins (PubMed:32485152). May play a role in the organization of
CC eyeball structure and lens development during eye development (By
CC similarity). {ECO:0000250|UniProtKB:Q3UQ28,
CC ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037,
CC ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:25708780,
CC ECO:0000269|PubMed:25713063, ECO:0000269|PubMed:27697841,
CC ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:32485152,
CC ECO:0000269|PubMed:32543734, ECO:0000269|PubMed:32571911,
CC ECO:0000269|PubMed:34679700}.
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 PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66021;
CC Evidence={ECO:0000269|PubMed:22842973};
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:25713063, ECO:0000269|PubMed:27697841,
CC ECO:0000269|PubMed:28154175, ECO:0000269|PubMed:29982533,
CC ECO:0000269|PubMed:32571911};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66017;
CC Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:28154175,
CC ECO:0000269|PubMed:32571911, ECO:0000305|PubMed:25713063,
CC ECO:0000305|PubMed:27697841};
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:27697841};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66025;
CC Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:27697841};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69361;
CC Evidence={ECO:0000269|PubMed:32571911};
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69357;
CC Evidence={ECO:0000269|PubMed:32571911};
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 Note=Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per
CC subunit. {ECO:0000255|PROSITE-ProRule:PRU00298};
CC -!- ACTIVITY REGULATION: The hypobromous acid formation is activated by
CC increasing nitrite concentrations and inhibited by increasing urate
CC concentrations. {ECO:0000269|PubMed:31953133}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.15 mM for H2O2 {ECO:0000269|PubMed:18929642};
CC KM=18.6 uM for H2O2 {ECO:0000269|PubMed:25713063};
CC KM=4.1 mM for bromide {ECO:0000269|PubMed:25713063};
CC KM=16.6 uM for H2O2 (homotrimeric enzymatic form)
CC {ECO:0000269|PubMed:29982533};
CC KM=4.1 uM for bromide (homotrimeric enzymatic form)
CC {ECO:0000269|PubMed:29982533};
CC -!- SUBUNIT: Homotrimer; disulfide-linked (PubMed:25708780,
CC PubMed:25713063, PubMed:29982533, PubMed:31295557, PubMed:32543734).
CC The homotrimer form is predominant (PubMed:25708780). Homooligomer;
CC disulfide-linked (PubMed:22842973, PubMed:25708780, PubMed:25713063,
CC PubMed:29982533, PubMed:31295557). Oligomerization occurs
CC intracellularly before C-terminal proteolytic cleavage
CC (PubMed:31295557). Interacts with PXDNL; this interaction inhibits the
CC peroxidase activity of PXDN (PubMed:24253521).
CC {ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:24253521,
CC ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:25713063,
CC ECO:0000269|PubMed:29982533, ECO:0000269|PubMed:31295557,
CC ECO:0000269|PubMed:32543734}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037,
CC ECO:0000269|PubMed:26178375, ECO:0000269|Ref.9}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:19590037, ECO:0000269|PubMed:25708780}. Cell
CC surface {ECO:0000269|PubMed:25708780}. Secreted, extracellular space,
CC extracellular matrix, basement membrane {ECO:0000250|UniProtKB:Q3UQ28}.
CC Note=Enriched in the peritubular space of fibrotic kidneys. Adheres on
CC the cell surface in 'hot spots' (PubMed:25708780). Only the
CC proteolytically processed PXDN integrates into the extracellular matrix
CC (PubMed:34679700). {ECO:0000269|PubMed:25708780,
CC ECO:0000269|PubMed:34679700}.
CC -!- SUBCELLULAR LOCATION: [PXDN active fragment]: Secreted, extracellular
CC space, extracellular matrix {ECO:0000269|PubMed:34679700}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q92626-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92626-2; Sequence=VSP_031516, VSP_031517;
CC -!- TISSUE SPECIFICITY: Expressed at higher levels in heart, lung, ovary,
CC spleen, intestine and placenta, and at lower levels in liver, colon,
CC pancreas, kidney, thymus, skeletal muscle and prostate. Expressed in
CC tumors such as melanoma, breast cancer, ovarian cancer and
CC glioblastoma. A shorter form probably lacking the signal sequence is
CC found in testis and in EB1 cells undergoing p53/TP53-dependent
CC apoptosis. {ECO:0000269|PubMed:10441517, ECO:0000269|PubMed:11103812,
CC ECO:0000269|PubMed:18929642, ECO:0000269|PubMed:19590037}.
CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver and spleen.
CC {ECO:0000269|PubMed:11103812}.
CC -!- INDUCTION: By TGFB1 in fibroblasts and up-regulated in apoptotic cells.
CC {ECO:0000269|PubMed:10441517, ECO:0000269|PubMed:19590037}.
CC -!- DOMAIN: The VWFC domain mediates the covalent links between monomers
CC throught disulfide bridges (PubMed:25713063). Ig-like C2-type domains
CC are required to sulfilimine bond formation (PubMed:26178375). The VWFC
CC domain is not required for trimerization (PubMed:31295557). The LRR
CC domain mediates high affinity binding to laminin-1 (PubMed:32485152).
CC {ECO:0000269|PubMed:25713063, ECO:0000269|PubMed:26178375,
CC ECO:0000269|PubMed:31295557, ECO:0000269|PubMed:32485152}.
CC -!- PTM: Glycosylated (PubMed:25713063). Four sites are completely N-
CC glycosylated (Asn-640, Asn-731, Asn-865 and Asn-1425), whereas the
CC others are found partially glycosylated (PubMed:25713063).
CC {ECO:0000269|PubMed:25713063}.
CC -!- PTM: Processed by FURIN and the proteolytic processing largely depends
CC on the peroxidase activity of PXDN (PubMed:27697841, PubMed:34679700).
CC The proteolytic cleavage occurs after intracellular homotrimerization
CC and releases into the extracellular matrix a large, catalytically
CC active fragment and a smaller fragment consisting primarily of the C-
CC terminal VWFC domain (PubMed:27697841, PubMed:31295557). The processing
CC enhances both peroxidase activity and sulfilimine cross-links formation
CC (PubMed:27697841, PubMed:34679700). {ECO:0000269|PubMed:27697841,
CC ECO:0000269|PubMed:31295557, ECO:0000269|PubMed:34679700}.
CC -!- DISEASE: Anterior segment dysgenesis 7 (ASGD7) [MIM:269400]: A form of
CC anterior segment dysgenesis, a group of defects affecting anterior
CC structures of the eye including cornea, iris, lens, trabecular
CC meshwork, and Schlemm canal. Anterior segment dysgeneses result from
CC abnormal migration or differentiation of the neural crest derived
CC mesenchymal cells that give rise to components of the anterior chamber
CC during eye development. Different anterior segment anomalies may exist
CC alone or in combination, including iris hypoplasia, enlarged or reduced
CC corneal diameter, corneal vascularization and opacity, posterior
CC embryotoxon, corectopia, polycoria, abnormal iridocorneal angle,
CC ectopia lentis, and anterior synechiae between the iris and posterior
CC corneal surface. Clinical conditions falling within the phenotypic
CC spectrum of anterior segment dysgeneses include aniridia, Axenfeld
CC anomaly, Reiger anomaly/syndrome, Peters anomaly, and
CC iridogoniodysgenesis. ASGD7 is an autosomal recessive disease.
CC {ECO:0000269|PubMed:21907015}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the peroxidase family. XPO subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00298}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAF06354.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAA13219.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF200348; AAF06354.1; ALT_INIT; mRNA.
DR EMBL; EF090903; ABO25865.1; -; mRNA.
DR EMBL; D86983; BAA13219.1; ALT_INIT; mRNA.
DR EMBL; CH471053; EAX01084.1; -; Genomic_DNA.
DR EMBL; CH471053; EAX01085.1; -; Genomic_DNA.
DR EMBL; BC098579; AAH98579.1; -; mRNA.
DR CCDS; CCDS46221.1; -. [Q92626-1]
DR RefSeq; NP_036425.1; NM_012293.2. [Q92626-1]
DR AlphaFoldDB; Q92626; -.
DR SMR; Q92626; -.
DR BioGRID; 113596; 88.
DR IntAct; Q92626; 23.
DR STRING; 9606.ENSP00000252804; -.
DR PeroxiBase; 3355; HsPxd01.
DR GlyConnect; 1600; 24 N-Linked glycans (6 sites).
DR GlyGen; Q92626; 13 sites, 29 N-linked glycans (6 sites), 1 O-linked glycan (1 site).
DR iPTMnet; Q92626; -.
DR PhosphoSitePlus; Q92626; -.
DR SwissPalm; Q92626; -.
DR BioMuta; PXDN; -.
DR DMDM; 172045828; -.
DR EPD; Q92626; -.
DR jPOST; Q92626; -.
DR MassIVE; Q92626; -.
DR MaxQB; Q92626; -.
DR PaxDb; Q92626; -.
DR PeptideAtlas; Q92626; -.
DR PRIDE; Q92626; -.
DR ProteomicsDB; 75381; -. [Q92626-1]
DR ProteomicsDB; 75382; -. [Q92626-2]
DR Antibodypedia; 2426; 63 antibodies from 14 providers.
DR DNASU; 7837; -.
DR Ensembl; ENST00000252804.9; ENSP00000252804.4; ENSG00000130508.11. [Q92626-1]
DR GeneID; 7837; -.
DR KEGG; hsa:7837; -.
DR MANE-Select; ENST00000252804.9; ENSP00000252804.4; NM_012293.3; NP_036425.1.
DR UCSC; uc002qxa.4; human. [Q92626-1]
DR CTD; 7837; -.
DR DisGeNET; 7837; -.
DR GeneCards; PXDN; -.
DR HGNC; HGNC:14966; PXDN.
DR HPA; ENSG00000130508; Low tissue specificity.
DR MalaCards; PXDN; -.
DR MIM; 269400; phenotype.
DR MIM; 605158; gene.
DR neXtProt; NX_Q92626; -.
DR OpenTargets; ENSG00000130508; -.
DR Orphanet; 289499; Congenital cataract microcornea with corneal opacity.
DR PharmGKB; PA128394535; -.
DR VEuPathDB; HostDB:ENSG00000130508; -.
DR eggNOG; KOG2408; Eukaryota.
DR GeneTree; ENSGT00940000157666; -.
DR HOGENOM; CLU_006087_0_1_1; -.
DR InParanoid; Q92626; -.
DR OMA; QHFKCAK; -.
DR OrthoDB; 276568at2759; -.
DR PhylomeDB; Q92626; -.
DR TreeFam; TF314316; -.
DR BRENDA; 1.11.1.7; 2681.
DR PathwayCommons; Q92626; -.
DR Reactome; R-HSA-2243919; Crosslinking of collagen fibrils.
DR SABIO-RK; Q92626; -.
DR SignaLink; Q92626; -.
DR SIGNOR; Q92626; -.
DR BioGRID-ORCS; 7837; 8 hits in 1066 CRISPR screens.
DR ChiTaRS; PXDN; human.
DR GeneWiki; PXDN; -.
DR GenomeRNAi; 7837; -.
DR Pharos; Q92626; Tbio.
DR PRO; PR:Q92626; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q92626; protein.
DR Bgee; ENSG00000130508; Expressed in stromal cell of endometrium and 190 other tissues.
DR ExpressionAtlas; Q92626; baseline and differential.
DR Genevisible; Q92626; HS.
DR GO; GO:0005604; C:basement membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005201; F:extracellular matrix structural constituent; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005152; F:interleukin-1 receptor antagonist activity; NAS:UniProtKB.
DR GO; GO:0043237; F:laminin-1 binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0070831; P:basement membrane assembly; IMP:UniProtKB.
DR GO; GO:0071711; P:basement membrane organization; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0030199; P:collagen fibril organization; IMP:FlyBase.
DR GO; GO:0030198; P:extracellular matrix organization; IDA:UniProtKB.
DR GO; GO:0001654; P:eye development; IEA:Ensembl.
DR GO; GO:0042744; P:hydrogen peroxide catabolic process; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IDA:UniProtKB.
DR GO; GO:0070207; P:protein homotrimerization; IDA: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; 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; 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 Alternative splicing; Basement membrane; Calcium;
KW Direct protein sequencing; Disease variant; Disulfide bond;
KW Endoplasmic reticulum; Extracellular matrix; Glycoprotein; Heme;
KW Hydrogen peroxide; Immunoglobulin domain; Iron; Leucine-rich repeat;
KW Metal-binding; Oxidoreductase; Peroxidase; Phosphoprotein;
KW Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1479
FT /note="Peroxidasin homolog"
FT /id="PRO_0000319619"
FT CHAIN 27..1336
FT /note="PXDN active fragment"
FT /evidence="ECO:0000269|PubMed:27697841,
FT ECO:0000269|PubMed:34679700"
FT /id="PRO_0000455175"
FT DOMAIN 27..63
FT /note="LRRNT"
FT REPEAT 61..84
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 85..108
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 110..132
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 133..156
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 157..180
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 182..204
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT DOMAIN 192..244
FT /note="LRRCT"
FT /evidence="ECO:0000255"
FT DOMAIN 246..332
FT /note="Ig-like C2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 342..428
FT /note="Ig-like C2-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 433..520
FT /note="Ig-like C2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DOMAIN 521..610
FT /note="Ig-like C2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT REPEAT 1151..1175
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 1270..1291
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT DOMAIN 1413..1471
FT /note="VWFC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00220"
FT REGION 1315..1411
FT /note="Required in homotrimerization"
FT /evidence="ECO:0000269|PubMed:31295557"
FT REGION 1342..1380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1362..1380
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 827
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 826
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 828
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 907
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 909
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 911
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 913
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 980
FT /ligand="heme b"
FT /ligand_id="ChEBI:CHEBI:60344"
FT /note="covalent"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT BINDING 1074
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 977
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"
FT SITE 1336
FT /note="Cleavage; by FURIN"
FT /evidence="ECO:0000269|PubMed:27697841,
FT ECO:0000269|PubMed:34679700"
FT MOD_RES 1176
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18318008"
FT MOD_RES 1180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18318008"
FT CARBOHYD 640
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 699
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 719
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 865
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 964
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:25713063"
FT CARBOHYD 1280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 1368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT CARBOHYD 1425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25713063"
FT DISULFID 36..42
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 40..49
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 196..243
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 198..222
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 267..317
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25713063"
FT DISULFID 363..412
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 454..502
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 546..594
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 723..885
FT /evidence="ECO:0000269|PubMed:25713063"
FT DISULFID 732..748
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25713063"
FT DISULFID 736
FT /note="Interchain (with C-1315); in homotrimer"
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:31295557"
FT DISULFID 847..857
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25713063"
FT DISULFID 851..875
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:25713063"
FT DISULFID 959..970
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 1177..1234
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25713063"
FT DISULFID 1275..1301
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:25713063"
FT DISULFID 1315
FT /note="Interchain (with C-736); in homotrimer"
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:31295557"
FT VAR_SEQ 703..727
FT /note="YHYNDLVSPQYLNLIANLSGCTAHR -> QCQSLFFLLHGLSNGVEHASVKS
FT HS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031516"
FT VAR_SEQ 728..1479
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_031517"
FT VARIANT 880
FT /note="R -> C (in ASGD7; dbSNP:rs587777572)"
FT /evidence="ECO:0000269|PubMed:21907015"
FT /id="VAR_071389"
FT VARIANT 1198
FT /note="R -> Q (in dbSNP:rs6723697)"
FT /id="VAR_050487"
FT VARIANT 1261
FT /note="Q -> R (in dbSNP:rs6723697)"
FT /id="VAR_039048"
FT MUTAGEN 736
FT /note="C->S: Loss of protein homooligomerization. Loss of
FT protein homooligomerization; when associated with S-1315.
FT Does not affect peroxidase activity; when associated with
FT S-1315. Retains the ability to support the collagen IV
FT cross-links; when associated with S-1315. Slightly reduces
FT proteolysis; when associated with S-1315."
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:34679700"
FT MUTAGEN 823
FT /note="Q->A: Loss of bromide oxidation. Loss of
FT tubulogenesis. Does not induce angiogenesis."
FT /evidence="ECO:0000269|PubMed:29982533"
FT MUTAGEN 823
FT /note="Q->W: Loss of peroxidase activity. Does not affect
FT oligomerization. Loss of peroxidase activity; when
FT associated with E-826. Does not support the formation of
FT collagen IV cross-links; when associated with E-826.
FT Reduces the proteolytic processing; when associated with E-
FT 826. Loss of collagen IV cross-link; when associated with
FT E-826."
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:34679700"
FT MUTAGEN 826
FT /note="D->E: Loss of peroxidase activity. Does not affect
FT oligomerization. Loss of peroxidase activity; when
FT associated with E-823. Does not support the formation of
FT collagen IV cross-links; when associated with W-823.
FT Reduces the proteolytic processing; when associated with W-
FT 823. Loss of collagen IV cross-link; when associated with
FT W-823."
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:34679700"
FT MUTAGEN 1315
FT /note="C->S: Loss of protein homooligomerization. Loss of
FT protein homooligomerization; when associated with S-1316
FT and S-1319. Loss of protein homooligomerization; when
FT associated with S-736. Does not affect peroxydase activity;
FT when associated with S-736. Affects cell surface location;
FT when associated with S-736. Slightly reduces proteolysis;
FT when associated with S-736."
FT /evidence="ECO:0000269|PubMed:25708780,
FT ECO:0000269|PubMed:34679700"
FT MUTAGEN 1316
FT /note="C->S: Does not affect protein homooligomerization.
FT Loss of protein homooligomerization; when associated with
FT S-1315 and S-1319."
FT /evidence="ECO:0000269|PubMed:25708780"
FT MUTAGEN 1319
FT /note="C->S: Does not affect protein homooligomerization.
FT Loss of protein homooligomerization; when associated with
FT S-1315 and S-1316."
FT /evidence="ECO:0000269|PubMed:25708780"
FT MUTAGEN 1335..1336
FT /note="RR->AA: Loss of proteolytic cleavage. Decreases the
FT formation of sulfilimine cross-links in collagen IV.
FT Reduces the proteolytic processing. Affects collagen IV
FT cross-linking."
FT /evidence="ECO:0000269|PubMed:27697841,
FT ECO:0000269|PubMed:34679700"
FT MUTAGEN 1354..1355
FT /note="RK->AA: Does not affect the proteolytic processing."
FT /evidence="ECO:0000269|PubMed:34679700"
SQ SEQUENCE 1479 AA; 165275 MW; 7A75F533D89C6AAD CRC64;
MAKRSRGPGR RCLLALVLFC AWGTLAVVAQ KPGAGCPSRC LCFRTTVRCM HLLLEAVPAV
APQTSILDLR FNRIREIQPG AFRRLRNLNT LLLNNNQIKR IPSGAFEDLE NLKYLYLYKN
EIQSIDRQAF KGLASLEQLY LHFNQIETLD PDSFQHLPKL ERLFLHNNRI THLVPGTFNH
LESMKRLRLD SNTLHCDCEI LWLADLLKTY AESGNAQAAA ICEYPRRIQG RSVATITPEE
LNCERPRITS EPQDADVTSG NTVYFTCRAE GNPKPEIIWL RNNNELSMKT DSRLNLLDDG
TLMIQNTQET DQGIYQCMAK NVAGEVKTQE VTLRYFGSPA RPTFVIQPQN TEVLVGESVT
LECSATGHPP PRISWTRGDR TPLPVDPRVN ITPSGGLYIQ NVVQGDSGEY ACSATNNIDS
VHATAFIIVQ ALPQFTVTPQ DRVVIEGQTV DFQCEAKGNP PPVIAWTKGG SQLSVDRRHL
VLSSGTLRIS GVALHDQGQY ECQAVNIIGS QKVVAHLTVQ PRVTPVFASI PSDTTVEVGA
NVQLPCSSQG EPEPAITWNK DGVQVTESGK FHISPEGFLT INDVGPADAG RYECVARNTI
GSASVSMVLS VNVPDVSRNG DPFVATSIVE AIATVDRAIN STRTHLFDSR PRSPNDLLAL
FRYPRDPYTV EQARAGEIFE RTLQLIQEHV QHGLMVDLNG TSYHYNDLVS PQYLNLIANL
SGCTAHRRVN NCSDMCFHQK YRTHDGTCNN LQHPMWGASL TAFERLLKSV YENGFNTPRG
INPHRLYNGH ALPMPRLVST TLIGTETVTP DEQFTHMLMQ WGQFLDHDLD STVVALSQAR
FSDGQHCSNV CSNDPPCFSV MIPPNDSRAR SGARCMFFVR SSPVCGSGMT SLLMNSVYPR
EQINQLTSYI DASNVYGSTE HEARSIRDLA SHRGLLRQGI VQRSGKPLLP FATGPPTECM
RDENESPIPC FLAGDHRANE QLGLTSMHTL WFREHNRIAT ELLKLNPHWD GDTIYYETRK
IVGAEIQHIT YQHWLPKILG EVGMRTLGEY HGYDPGINAG IFNAFATAAF RFGHTLVNPL
LYRLDENFQP IAQDHLPLHK AFFSPFRIVN EGGIDPLLRG LFGVAGKMRV PSQLLNTELT
ERLFSMAHTV ALDLAAINIQ RGRDHGIPPY HDYRVYCNLS AAHTFEDLKN EIKNPEIREK
LKRLYGSTLN IDLFPALVVE DLVPGSRLGP TLMCLLSTQF KRLRDGDRLW YENPGVFSPA
QLTQIKQTSL ARILCDNADN ITRVQSDVFR VAEFPHGYGS CDEIPRVDLR VWQDCCEDCR
TRGQFNAFSY HFRGRRSLEF SYQEDKPTKK TRPRKIPSVG RQGEHLSNST SAFSTRSDAS
GTNDFREFVL EMQKTITDLR TQIKKLESRL STTECVDAGG ESHANNTKWK KDACTICECK
DGQVTCFVEA CPPATCAVPV NIPGACCPVC LQKRAEEKP
