Azurocidin 1
Azurocidin also known as cationic antimicrobial protein CAP37 or heparin-binding protein (HBP) is a protein that in humans is encoded by the AZU1 gene.[3][4]
Function
Azurophil granules, specialized lysosomes of the neutrophil, contain at least 10 proteins implicated in the killing of microorganisms. The protein encoded by this gene is an azurophil granule antimicrobial protein, with monocyte chemotactic and antibacterial activity. It is also an important multifunctional inflammatory mediator.[5] The genes encoding this protein, neutrophil elastase 2, and proteinase 3 are in a cluster located at chromosome 19pter. All 3 genes are expressed coordinately and their protein products are packaged together into azurophil granules during neutrophil differentiation.[4]
Structure

This encoded protein is a member of the PA clan of proteases but it is not a serine proteinase, because the active site serine and histidine residues are replaced, making it a pseudoenzyme.[6]
Clinical significance
In patients with fever, high plasma levels of HBP indicates that the patient is at high risk of developing sepsis with circulatory collapse.[7]
References
- 1 2 3 ENSG00000172232 GRCh38: Ensembl release 89: ENSG00000278624, ENSG00000172232 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Morgan JG, Sukiennicki T, Pereira HA, Spitznagel JK, Guerra ME, Larrick JW (November 1991). "Cloning of the cDNA for the serine protease homolog CAP37/azurocidin, a microbicidal and chemotactic protein from human granulocytes". Journal of Immunology. 147 (9). Baltimore: 3210–3214. doi:10.4049/jimmunol.147.9.3210. PMID 1919011.
- 1 2 "Entrez Gene: AZU1 azurocidin 1 (cationic antimicrobial protein 37)".
- ↑ Soehnlein O, Lindbom L (March 2009). "Neutrophil-derived azurocidin alarms the immune system". Journal of Leukocyte Biology. 85 (3): 344–351. doi:10.1189/jlb.0808495. PMID 18955543. S2CID 23637918.
- ↑ Iversen LF, Kastrup JS, Bjørn SE, Rasmussen PB, Wiberg FC, Flodgaard HJ, et al. (April 1997). "Structure of HBP, a multifunctional protein with a serine proteinase fold". Nature Structural Biology. 4 (4): 265–268. doi:10.1038/nsb0497-265. PMID 9095193. S2CID 19949043.
- ↑ Linder A, Christensson B, Herwald H, Björck L, Akesson P (October 2009). "Heparin-binding protein: an early marker of circulatory failure in sepsis". Clinical Infectious Diseases. 49 (7): 1044–1050. doi:10.1086/605563. PMID 19725785.
External links
- Human AZU1 genome location and AZU1 gene details page in the UCSC Genome Browser.
Further reading
- Morgan JG, Pereira HA, Sukiennicki T, et al. (1992). "Human Neutrophil Granule Cationic Protein CAP37 is a Specific Macrophage Chemotaxin that Shares Homology with Inflammatory Proteinases". Chemotactic Cytokines. Advances in Experimental Medicine and Biology. Vol. 305. pp. 89–96. doi:10.1007/978-1-4684-6009-4_11. ISBN 978-1-4684-6011-7. PMID 1755383.
- Watorek W (2003). "Azurocidin -- inactive serine proteinase homolog acting as a multifunctional inflammatory mediator". Acta Biochimica Polonica. 50 (3): 743–752. doi:10.18388/abp.2003_3665. PMID 14515154.
- Zimmer M, Medcalf RL, Fink TM, Mattmann C, Lichter P, Jenne DE (September 1992). "Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter". Proceedings of the National Academy of Sciences of the United States of America. 89 (17): 8215–8219. Bibcode:1992PNAS...89.8215Z. doi:10.1073/pnas.89.17.8215. PMC 49888. PMID 1518849.
- Green BG, Weston H, Ashe BM, Doherty J, Finke P, Hagmann W, et al. (April 1991). "PMN elastases: a comparison of the specificity of human isozymes and the enzyme from other species toward substrates and inhibitors". Archives of Biochemistry and Biophysics. 286 (1): 284–292. doi:10.1016/0003-9861(91)90042-H. PMID 1897955.
- Flodgaard H, Ostergaard E, Bayne S, Svendsen A, Thomsen J, Engels M, et al. (April 1991). "Covalent structure of two novel neutrophile leucocyte-derived proteins of porcine and human origin. Neutrophile elastase homologues with strong monocyte and fibroblast chemotactic activities". European Journal of Biochemistry. 197 (2): 535–547. doi:10.1111/j.1432-1033.1991.tb15942.x. PMID 2026172.
- Almeida RP, Melchior M, Campanelli D, Nathan C, Gabay JE (June 1991). "Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases". Biochemical and Biophysical Research Communications. 177 (2): 688–695. Bibcode:1991BBRC..177..688A. doi:10.1016/0006-291X(91)91843-2. PMID 2049091.
- Pohl J, Pereira HA, Martin NM, Spitznagel JK (1990). "Amino acid sequence of CAP37, a human neutrophil granule-derived antibacterial and monocyte-specific chemotactic glycoprotein structurally similar to neutrophil elastase". FEBS Letters. 272 (1–2): 200–204. Bibcode:1990FEBSL.272..200P. doi:10.1016/0014-5793(90)80484-Z. PMID 2226832. S2CID 36779510.
- Campanelli D, Detmers PA, Nathan CF, Gabay JE (1990). "Azurocidin and a homologous serine protease from neutrophils. Differential antimicrobial and proteolytic properties". The Journal of Clinical Investigation. 85 (3): 904–915. doi:10.1172/JCI114518. PMC 296509. PMID 2312733.
- Pereira HA, Shafer WM, Pohl J, Martin LE, Spitznagel JK (May 1990). "CAP37, a human neutrophil-derived chemotactic factor with monocyte specific activity". The Journal of Clinical Investigation. 85 (5): 1468–1476. doi:10.1172/JCI114593. PMC 296594. PMID 2332502.
- Wilde CG, Snable JL, Griffith JE, Scott RW (1990). "Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase". The Journal of Biological Chemistry. 265 (4): 2038–2041. doi:10.1016/S0021-9258(19)39936-3. PMID 2404977.
- Pereira HA, Spitznagel JK, Pohl J, Wilson DE, Morgan J, Palings I, et al. (1990). "CAP 37, a 37 kD human neutrophil granule cationic protein shares homology with inflammatory proteinases". Life Sciences. 46 (3): 189–196. doi:10.1016/0024-3205(90)90104-Y. PMID 2406527.
- Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, et al. (July 1989). "Antibiotic proteins of human polymorphonuclear leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 86 (14): 5610–5614. Bibcode:1989PNAS...86.5610G. doi:10.1073/pnas.86.14.5610. PMC 297672. PMID 2501794.
- Pereira HA, Erdem I, Pohl J, Spitznagel JK (1993). "Synthetic bactericidal peptide based on CAP37: a 37-kDa human neutrophil granule-associated cationic antimicrobial protein chemotactic for monocytes". Proceedings of the National Academy of Sciences of the United States of America. 90 (10): 4733–4737. Bibcode:1993PNAS...90.4733P. doi:10.1073/pnas.90.10.4733. PMC 46587. PMID 8506327.
- Chertov O, Michiel DF, Xu L, Wang JM, Tani K, Murphy WJ, et al. (February 1996). "Identification of defensin-1, defensin-2, and CAP37/azurocidin as T-cell chemoattractant proteins released from interleukin-8-stimulated neutrophils". The Journal of Biological Chemistry. 271 (6): 2935–2940. doi:10.1074/jbc.271.6.2935. PMID 8621683.
- Karlsen S, Iversen LF, Larsen IK, Flodgaard HJ, Kastrup JS (July 1998). "Atomic resolution structure of human HBP/CAP37/azurocidin". Acta Crystallographica. Section D, Biological Crystallography. 54 (Pt 4): 598–609. Bibcode:1998AcCrD..54..598K. doi:10.1107/S0907444997016193. PMID 9761855.
- Olofsson AM, Vestberg M, Herwald H, Rygaard J, David G, Arfors KE, et al. (October 1999). "Heparin-binding protein targeted to mitochondrial compartments protects endothelial cells from apoptosis". The Journal of Clinical Investigation. 104 (7): 885–894. doi:10.1172/JCI6671. PMC 408551. PMID 10510329.
- Lindmark A, Garwicz D, Rasmussen PB, Flodgaard H, Gullberg U (October 1999). "Characterization of the biosynthesis, processing, and sorting of human HBP/CAP37/azurocidin". Journal of Leukocyte Biology. 66 (4): 634–643. doi:10.1002/jlb.66.4.634. PMID 10534120. S2CID 27897421.






![1fy1: [R23S,F25E]HBP, A MUTANT OF HUMAN HEPARIN BINDING PROTEIN (CAP37)](./_assets_/0c70a452f799bfe840676ee341124611/PDB_1fy1_EBI.jpg)
![1fy3: [G175Q]HBP, A MUTANT OF HUMAN HEPARIN BINDING PROTEIN (CAP37)](./_assets_/0c70a452f799bfe840676ee341124611/PDB_1fy3_EBI.jpg)