| IED ID | IndEnz0018001341 |
| Enzyme Type ID | peroxidase001341 |
| Protein Name |
Peroxidasin homolog EC 1.11.2.- Cleaved into: PXDN active fragment |
| Gene Name | Pxdn Kiaa0230 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAVRPTRRCLLALLLCFAWWAMAVVASKQGAGCPSRCLCFRTTVRCMHLLLEAVPAVAPQTSILDLRFNRIREIQPGAFRRLRSLNTLLLNNNQIKKIPNGAFEDLENLKYLYLYKNEIQSIDRQAFKGLASLEQLYLHFNQIETLDPESFQHLPKLERLFLHNNRITHLVPGTFSQLESMKRLRLDSNALHCDCEILWLADLLKTYAQSGNAQAAATCEYPRRIQGRSVATITPEELNCERPRITSEPQDADVTSGNTVYFTCRAEGNPKPEIIWLRNNNELSMKTDSRLNLLDDGTLMIQNTQEADEGVYQCMAKNVAGEAKTQEVTLRYLGSPARPTFVIQPQNTEVLVGESVTLECSATGHPLPQITWTRGDRTPLPIDPRVNITPSGGLYIQNVAQSDSGEYTCFASNSVDSIHATAFIIVQALPQFTVTPQSRVVIEGQTVDFQCAAKGHPQPVIAWTKGGSQLSVDRRHLVLSSGTLRISGVALHDQGQYECQAVNIIGSQKVVAHLTVQPRVTPVFASIPSDMTVEVGTNVQLPCSSQGEPEPAITWNKDGVQVTESGKFHISPEGFLTINDVGTADAGRYECVARNTIGYASVSMVLSVNVPDVSRNGDPYVATSIVEAIATVDRAINSTRTHLFDSRPRSPNDLLALFRYPRDPYTVGQARAGEIFERTLQLIQEHVQHGLMVDLNGTSYHYNDLVSPQYLSLIANLSGCTAHRRVNNCSDMCFHQKYRTHDGTCNNLQHPMWGASLTAFERLLKAVYENGFNTPRGINSQRQYNGHVLPMPRLVSTTLIGTEVITPDEQFTHMLMQWGQFLDHDLDSTVVALSQARFSDGQHCSSVCSNDPPCFSVMIPPNDPRVRSGARCMFFVRSSPVCGSGMTSLLMNSVYPREQINQLTSYIDASNVYGSTDHEARSIRDLASHRGLLRQGIVQRSGKPLLPFATGPPTECMRDENESPIPCFLAGDHRANEQLGLTSMHTLWFREHNRIAAELLKLNPHWDGDTVYHETRKIVGAEIQHITYRHWLPKILGEVGMKMLGEYRGYDPSVNAGIFNAFATAAFRFGHTLINPLLYRLDENFEPIPQGHVPLHKAFFSPFRIVNEGGIDPLLRGLFGVAGKMRIPSQLLNTELTERLFSMAHTVALDLAAINIQRGRDHGIPPYHDYRVYCNLSAAYTFEDLKNEIKSPVIREKLQRLYGSTLNIDLFPALMVEDLVPGSRLGPTLMCLLSTQFRRLRDGDRLWYENPGVFSPAQLTQLKQTSLARILCDNSDNITRVQQDVFRVAEFPHGYSSCEDIPRVDLRVWQDCCEDCRTRGQFNAFSYHFRGRRSLEFSYEDDKPTKRARWRKALSVKHGKHLSNATSATHEHLEGPATNDLKEFVLEMQKIITDLRKQINSLESRLSTTECVDDSGESHGGNTKWKKDPCTVCECKNGQITCFVEACQPAACPQPVKVEGACCPVCLKNTAEEKP |
| Enzyme Length | 1475 |
| Uniprot Accession Number | Q3UQ28 |
| Absorption | |
| Active Site | ACT_SITE 824; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Activity Regulation | ACTIVITY REGULATION: Thiocyanate inhibits the formation of 3-bromotyrosine. {ECO:0000269|PubMed:32675287}. |
| Binding Site | BINDING 823; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00298"; BINDING 977; /note="Heme b; covalent, via 2 links"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00298" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=H2O2 + L-lysyl-[collagen] + L-methionyl-[collagen] = [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + H(+) + 2 H2O; Xref=Rhea:RHEA:66020, Rhea:RHEA-COMP:12751, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16044, ChEBI:CHEBI:16240, ChEBI:CHEBI:29969, ChEBI:CHEBI:166867; Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66021; Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535}; CATALYTIC ACTIVITY: Reaction=bromide + H2O2 = H2O + hypobromite; Xref=Rhea:RHEA:66016, ChEBI:CHEBI:15377, ChEBI:CHEBI:15858, ChEBI:CHEBI:16240, ChEBI:CHEBI:29250; Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287, ECO:0000305|PubMed:28424209, ECO:0000305|PubMed:31817535};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66017; Evidence={ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287}; CATALYTIC ACTIVITY: Reaction=hypobromite + L-lysyl-[collagen] + L-methionyl-[collagen] = [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + bromide + H(+) + H2O; Xref=Rhea:RHEA:66024, Rhea:RHEA-COMP:12751, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:16044, ChEBI:CHEBI:29250, ChEBI:CHEBI:29969, ChEBI:CHEBI:166867; Evidence={ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:29626421, ECO:0000305|PubMed:28424209, ECO:0000305|PubMed:31817535};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66025; Evidence={ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535, ECO:0000305|PubMed:22842973}; CATALYTIC ACTIVITY: Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + hypobromite + L-methionyl-[collagen] = [collagen]-(5R)-5-hydroxy-L-lysyl-N-S-L-methionyl-[collagen] + bromide + H(+) + H2O; Xref=Rhea:RHEA:66012, Rhea:RHEA-COMP:12752, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16950, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:16044, ChEBI:CHEBI:29250, ChEBI:CHEBI:133442, ChEBI:CHEBI:166866; Evidence={ECO:0000269|PubMed:22842973};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66013; Evidence={ECO:0000305|PubMed:22842973}; CATALYTIC ACTIVITY: Reaction=(5R)-5-hydroxy-L-lysyl-[collagen] + H2O2 + L-methionyl-[collagen] = [collagen]-(5R)-5-hydroxy-L-lysyl-N-S-L-methionyl-[collagen] + H(+) + 2 H2O; Xref=Rhea:RHEA:66008, Rhea:RHEA-COMP:12752, Rhea:RHEA-COMP:16949, Rhea:RHEA-COMP:16950, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16044, ChEBI:CHEBI:16240, ChEBI:CHEBI:133442, ChEBI:CHEBI:166866; Evidence={ECO:0000269|PubMed:22842973}; CATALYTIC ACTIVITY: Reaction=bromide + H(+) + H2O2 + L-tyrosyl-[protein] = 3-bromo-L-tyrosyl-[protein] + 2 H2O; Xref=Rhea:RHEA:69360, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:17686, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15858, ChEBI:CHEBI:16240, ChEBI:CHEBI:46858, ChEBI:CHEBI:183512; Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69361; Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287}; CATALYTIC ACTIVITY: Reaction=H(+) + hypobromite + L-tyrosyl-[protein] = 3-bromo-L-tyrosyl-[protein] + H2O; Xref=Rhea:RHEA:69356, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:17686, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29250, ChEBI:CHEBI:46858, ChEBI:CHEBI:183512; Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69357; Evidence={ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287}; |
| DNA Binding | |
| EC Number | 1.11.2.- |
| Enzyme Function | FUNCTION: Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer (PubMed:31817535, PubMed:22842973, PubMed:29626421, PubMed:25708780, PubMed:28424209). In turns, directly contributes to the collagen IV network-dependent fibronectin/FN and laminin assembly, which is required for full extracellular matrix (ECM)-mediated signaling (By similarity). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (By similarity). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (By similarity). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1480' and leads to bromine enrichment of the basement membranes (PubMed:32675287, PubMed:32571911). In vitro, can also catalyze the two-electron oxidation of thiocyanate and iodide and these two substrates could effectively compete with bromide and thus inhibit the formation of sulfilimine bonds (By similarity). Binds laminins (By similarity). May play a role in the organization of eyeball structure and lens development during eye development (PubMed:31817535, PubMed:24895407). {ECO:0000250|UniProtKB:Q92626, ECO:0000269|PubMed:22842973, ECO:0000269|PubMed:24895407, ECO:0000269|PubMed:25708780, ECO:0000269|PubMed:28424209, ECO:0000269|PubMed:29626421, ECO:0000269|PubMed:31817535, ECO:0000269|PubMed:32571911, ECO:0000269|PubMed:32675287}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Binding site (2); Chain (2); Disulfide bond (17); Domain (7); Glycosylation (9); Metal binding (6); Modified residue (2); Mutagenesis (1); Region (1); Repeat (9); Sequence conflict (2); Signal peptide (1); Site (2) |
| Keywords | Basement membrane;Calcium;Disulfide bond;Endoplasmic reticulum;Extracellular matrix;Glycoprotein;Heme;Hydrogen peroxide;Immunoglobulin domain;Iron;Leucine-rich repeat;Metal-binding;Oxidoreductase;Peroxidase;Phosphoprotein;Reference proteome;Repeat;Secreted;Signal |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000269|PubMed:19590037}. Endoplasmic reticulum {ECO:0000250|UniProtKB:Q92626}. Cell surface {ECO:0000250|UniProtKB:Q92626}. Secreted, extracellular space, extracellular matrix, basement membrane {ECO:0000269|PubMed:22842973}. Note=Adheres on the cell surface in 'hot spots'. {ECO:0000250|UniProtKB:Q92626}.; SUBCELLULAR LOCATION: [PXDN active fragment]: Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:Q92626}. |
| Modified Residue | MOD_RES 1173; /note=Phosphotyrosine; /evidence=ECO:0000250|UniProtKB:Q92626; MOD_RES 1177; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q92626 |
| Post Translational Modification | PTM: Processed by FURIN and the proteolytic processing largely depends on the peroxidase activity of PXDN (PubMed:34679700). The proteolytic cleavage occurs after intracellular homotrimerization and releases into the extracellular matrix a large, catalytically active fragment and a smaller fragment consisting primarily of the C-terminal VWFC domain. The processing enhances both peroxidase activity and sulfilimine cross-links formation (By similarity). {ECO:0000250|UniProtKB:Q92626, ECO:0000269|PubMed:34679700}. |
| Signal Peptide | SIGNAL 1..23; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 10725249; 10932192; 11217851; 12466851; 12693553; 15031102; 21267068; 22159717; 24006456; 25826454; 27121343; 27167346; 27619726; 27689697; 28071719; 29775486; 30371171; 30565999; 30844643; |
| Motif | |
| Gene Encoded By | |
| Mass | 165,103 |
| Kinetics | |
| Metal Binding | METAL 825; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 904; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 906; /note=Calcium; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 908; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 910; /note=Calcium; /evidence=ECO:0000255|PROSITE-ProRule:PRU00298; METAL 1071; /note=Iron (heme b axial ligand); /evidence=ECO:0000255|PROSITE-ProRule:PRU00298 |
| Rhea ID | RHEA:66020; RHEA:66021; RHEA:66016; RHEA:66017; RHEA:66024; RHEA:66025; RHEA:66012; RHEA:66013; RHEA:66008; RHEA:69360; RHEA:69361; RHEA:69356; RHEA:69357 |
| Cross Reference Brenda |