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Details on Person UniProt:Q92626 PXDN
| Class:Id | ReferenceGeneProduct:244432 |
|---|---|
| _chainChangeLog | signal peptide:1-26 added on Sat February 7 2015;chain:27-1479 added on Sat February 7 2015;chain:27-1336 for 244432 added on Mon August 15 2022 |
| _displayName | UniProt:Q92626 PXDN |
| _timestamp | 2025-02-21 19:00:47 |
| chain | signal peptide:1-26 chain:27-1479 chain:27-1336 |
| checksum | 7A75F533D89C6AAD |
| comment | 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:18929642, PubMed:19590037, PubMed:22842973, PubMed:25708780, PubMed:25713063, PubMed:27697841, PubMed:28154175, PubMed:34679700). 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 (PubMed:19590037, PubMed:32543734, PubMed:34679700). Thus, sulfilimine cross-links are essential for growth factor-induced cell proliferation and survival in endothelial cells, an event essential to basement membrane integrity (PubMed:32543734). In addition, through the bromide oxidation, may promote tubulogenesis and induce angiogenesis through ERK1/2, Akt, and FAK pathways (PubMed:25713063). Moreover brominates alpha2 collagen IV chain/COL4A2 at 'Tyr-1485' and leads to bromine enrichment of the basement membranes (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 (PubMed:28154175). Binds laminins (PubMed:32485152). May play a role in the organization of eyeball structure and lens development during eye development (By similarity).CATALYTIC ACTIVITY L-lysyl-[collagen] + L-methionyl-[collagen] + H2O2 = [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + 2 H2O + H(+)CATALYTIC ACTIVITY bromide + H2O2 = hypobromite + H2OCATALYTIC ACTIVITY L-lysyl-[collagen] + L-methionyl-[collagen] + hypobromite = [collagen]-L-lysyl-N-S-L-methionyl-[collagen] + bromide + H2O + H(+)CATALYTIC ACTIVITY L-tyrosyl-[protein] + bromide + H2O2 + H(+) = 3-bromo-L-tyrosyl-[protein] + 2 H2OCATALYTIC ACTIVITY hypobromite + L-tyrosyl-[protein] + H(+) = 3-bromo-L-tyrosyl-[protein] + H2OCOFACTOR Binds 1 Ca(2+) ion per subunit.COFACTOR Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per subunit.ACTIVITY REGULATION The hypobromous acid formation is activated by increasing nitrite concentrations and inhibited by increasing urate concentrations.BIOPHYSICOCHEMICAL PROPERTIES Homotrimer; disulfide-linked (PubMed:25708780, PubMed:25713063, PubMed:29982533, PubMed:31295557, PubMed:32543734). The homotrimer form is predominant (PubMed:25708780). Homooligomer; disulfide-linked (PubMed:22842973, PubMed:25708780, PubMed:25713063, PubMed:29982533, PubMed:31295557). Oligomerization occurs intracellularly before C-terminal proteolytic cleavage (PubMed:31295557). Interacts with PXDNL; this interaction inhibits the peroxidase activity of PXDN (PubMed:24253521).SUBCELLULAR LOCATION Enriched in the peritubular space of fibrotic kidneys. Adheres on the cell surface in 'hot spots' (PubMed:25708780). Only the proteolytically processed PXDN integrates into the extracellular matrix (PubMed:34679700).SUBCELLULAR LOCATION Additional isoforms seem to exist.TISSUE SPECIFICITY Expressed at higher levels in heart, lung, ovary, spleen, intestine and placenta, and at lower levels in liver, colon, pancreas, kidney, thymus, skeletal muscle and prostate. Expressed in tumors such as melanoma, breast cancer, ovarian cancer and glioblastoma. A shorter form probably lacking the signal sequence is found in testis and in EB1 cells undergoing p53/TP53-dependent apoptosis.DEVELOPMENTAL STAGE Expressed in fetal liver and spleen.INDUCTION By TGFB1 in fibroblasts and up-regulated in apoptotic cells.DOMAIN The VWFC domain mediates the covalent links between monomers through disulfide bridges (PubMed:25713063). Ig-like C2-type domains are required to sulfilimine bond formation (PubMed:26178375). The VWFC domain is not required for trimerization (PubMed:31295557). The LRR domain mediates high affinity binding to laminin-1 (PubMed:32485152).PTM Glycosylated (PubMed:25713063). Four sites are completely N-glycosylated (Asn-640, Asn-731, Asn-865 and Asn-1425), whereas the others are found partially glycosylated (PubMed:25713063).PTM Processed by FURIN and the proteolytic processing largely depends on the peroxidase activity of PXDN (PubMed:27697841, 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 (PubMed:27697841, PubMed:31295557). The processing enhances both peroxidase activity and sulfilimine cross-links formation (PubMed:27697841, PubMed:34679700).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the peroxidase family. XPO subfamily. |
| created | [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 |
| description | recommendedName: fullName evidence="30"Peroxidasin homolog ecNumber evidence="13 18 19 20 25"1.11.2.- alternativeName: Melanoma-associated antigen MG50 alternativeName: fullName evidence="29"Peroxidasin 1 shortName evidence="29"hsPxd01 alternativeName: Vascular peroxidase 1 alternativeName: p53-responsive gene 2 protein component recommendedName: fullName evidence="32"PXDN active fragment /component |
| geneName | PXDN KIAA0230 MG50 PRG2 PXD01 VPO VPO1 |
| identifier | Q92626 |
| isSequenceChanged | FALSE |
| keyword | Alternative splicing Basement membrane Calcium Direct protein sequencing Disease variant Disulfide bond Endoplasmic reticulum Extracellular matrix Glycoprotein Heme Hydrogen peroxide Immunoglobulin domain Iron Leucine-rich repeat Metal-binding Oxidoreductase Peroxidase Phosphoprotein Proteomics identification Reference proteome Repeat Secreted Signal |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | PXDN |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8961045] ENSEMBL:ENSG00000130508 PXDN [Homo sapiens] |
| secondaryIdentifier | PXDN_HUMAN A8QM65 D6W4Y0 Q4KMG2 |
| sequenceLength | 1479 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:244433] UniProt:Q92626-2 PXDN [Homo sapiens] [ReferenceIsoform:412471] UniProt:Q92626-1 PXDN [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:2559628] PXDN [extracellular region] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q92626 PXDN (244432)
