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söndag 14 juni 2020

Lysyloxidaasi LOX, AAT10

 18.6. 2020 Lisäkökohtia lysyylioksidaasista. Sen merkitys megakaryosyytille.  tänään tulelessa ruotsalaisessa lääkärilehdessä kerrotiin Covid-19 histopatologiasta ja mainittiin megakaryosyytin kaltaisten  ja histiosytääristen jättisolujen havaintoja alveolaaritilasta.

https://pubmed.ncbi.nlm.nih.gov/22767499/#&gid=article-figures&pid=figure-2-uid-1
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3433087/bin/zh89991295250002.jpg
Abstract
Megakaryocytes (MKs), the platelet precursors, are capable of accumulating DNA greater than a diploid content as part of their cell cycle. MKs have been recognized as mediating fibrosis in a subset of hematologic malignancies, including acute megakaryoblastic leukemia and a subset of myeloproliferative neoplasms. The mechanisms responsible for fibrosis remain only partially understood. Past studies highlighted the role of growth factors in such pathologies, and recently, the protein lysyl oxidase (LOX) has been implicated in proliferation of MKs, ploidy and deposition of fibers. LOX was initially characterized as a protein responsible for the intermolecular cross-linking of elastin and collagen, and in recent years it has been identified as regulator of various pathologies, such as cancer and inflammation. Here, we review recent advances in the understanding of the contribution of MKs to the progression of myelofibrosis, highlighting the newly identified role of LOX.
https://ashpublications.org/blood/article/120/9/1774/30861/Megakaryocyte-pathology-and-bone-marrow-fibrosis


 14.6. 2020

https://www.genecards.org/cgi-bin/carddisp.pl?gene=LOX&keywords=LOX
 This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections. [provided by RefSeq, Jul 2016] GeneCards Summary for LOX Gene
LOX (Lysyl Oxidase) is a Protein Coding gene. Diseases associated with LOX include Aortic Aneurysm, Familial Thoracic 10 and Familial Thoracic Aortic Aneurysm And Dissection. Among its related pathways are Degradation of the extracellular matrix and Elastic fibre formation. Gene Ontology (GO) annotations related to this gene include copper ion binding and protein-lysine 6-oxidase activity. An important paralog of this gene is LOXL1.
UniProtKB/Swiss-Prot Summary for LOX Gene
Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin (PubMed:26838787). Regulator of Ras expression. May play a role in tumor suppression. Plays a role in the aortic wall architecture (By similarity). LYOX_HUMAN,P28300
Post-translational modifications for LOX Gene
  • The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.
  • Proteolytically cleaved by BMP1 which removes the propeptide (PubMed:31152061). Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site (PubMed:31152061). The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin (By similarity). Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen (PubMed:31152061). Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity (PubMed:31152061).
  • Sulfated at Tyr-187 and also at either Tyr-183 or Tyr-184 which enhances binding to collagen.
  • Glycosylation at Asn81, Thr89, Asn97, Thr113, Thr120, Ser130, Thr131, Ser132, Asn144, and Thr413
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • LYOX_HUMAN (816)

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