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PTX3
Identifiers
Aliases	PTX3, TNFAIP5, TSG-14, pentraxin 3
External IDs	OMIM: 602492; MGI: 104641; HomoloGene: 7500; GeneCards: PTX3; OMA:PTX3 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3q25.32 Start 157,436,850 bp End 157,443,633 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 E1|3 30.25 cM Start 66,127,331 bp End 66,133,226 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cartilage tissue pericardium trabecular bone bone marrow tibia testicle gastric mucosa lower lobe of lung bone marrow cells stromal cell of endometrium Top expressed in stroma of bone marrow gastrula dermis triceps brachii muscle sternocleidomastoid muscle temporal muscle vastus lateralis muscle maxillary prominence ventricular zone calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function (1->3)-beta-D-glucan binding virion binding complement component C1q complex binding protein binding identical protein binding Cellular component extracellular region specific granule lumen tertiary granule lumen extracellular space extracellular matrix Biological process positive regulation of nitric oxide biosynthetic process negative regulation of glycoprotein metabolic process positive regulation of phagocytosis negative regulation of exo-alpha-sialidase activity response to yeast innate immune response inflammatory response opsonization neutrophil degranulation ovarian cumulus expansion extracellular matrix organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5806 19288 Ensembl ENSG00000163661 ENSMUSG00000027832 UniProt P26022 P48759 RefSeq (mRNA) NM_002852 NM_008987 RefSeq (protein) NP_002843 NP_033013 Location (UCSC) Chr 3: 157.44 – 157.44 Mb Chr 3: 66.13 – 66.13 Mb PubMed search
Wikidata
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Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene.

Pentraxin 3 (ptx3) is a member of the pentraxin superfamily. This super family characterized by cyclic multimeric structure. PTX3 is rapidly produced and released by several cell types, in particular by mononuclear phagocytes, dendritic cells (DCs), fibroblasts and endothelial cells in response to primary inflammatory signals . PTX3 binds with high affinity to the complement component C1q, the extracellular matrix component TNFα induced protein 6 (TNFAIP6; also called TNF-stimulated gene 6, TSG-6) and selected microorganisms, including Aspergillus fumigatus and Pseudomonas aeruginosa.

PTX3 activates the classical pathway of complement activation and facilitates pathogen recognition by macrophages and DCs.

Structure

Human and murine PTX3, localized in the syntenic region of chromosome 3 (q24-28), are highly conserved, sharing 82% identical and 92% conserved amino acids. The human PTX3 gene is organized into three exons coding for the leader peptide (which is cleaved from the mature protein), the amino-terminal domain and the pentraxin domain of the protein.

The transcribed PTX3 protein is 381 amino acids long, has a predicted molecular weight of 40,165 Da and consists of a carboxy-terminal 203 amino acid long pentraxin domain coupled with an amino-terminal 178 amino acid long domain unrelated to other known proteins. The PTX3 carboxy-terminal domain contains a canonical pentraxin signature (HxCxS/TWxS) and two conserved cysteines (Cys-210 and Cys-271), and shares 57% conserved and 17% identical amino acids with short pentraxins. The presence of an amino-linked glycosylation site in the carboxy-terminal domain at Asn-220 accounts for the higher molecular weight observed in SDS–PAGE under reducing conditions (45 kDa as opposed to the predicted 40 kDa). Under native conditions PTX3 protomers are assembled to form multimers. The crystal structure of PTX3 has not been determined yet, however according to modeling, the PTX3 pentraxin domain well-accommodates on the tertiary fold of SAP, with almost all of the β-strands and the α-helical segments conserved.

PTX3 in blood

PTX3 behaves as an acute phase response protein, as the blood levels of PTX3, low in normal conditions (about 25 ng/mL in the mouse, < 2 ng/mL in humans), increase rapidly (peaking at 6–8 h after induction) and dramatically (200–800 ng/mL) during endotoxic shock, sepsis and other inflammatory and infectious conditions, correlating with the severity of the disease. PTX3 levels in cerebrospinal fluid help distinguishing between bacterial and aseptic meningoencephalitis. Under these conditions, PTX3 is a rapid marker for primary local activation of innate immunity and inflammation.

Pathogen versus apoptotic self recognition

Similar to other members of the pentraxin family PTX3 binds apoptotic cells, thereby inhibiting their recognition by DCs. Binding occurs late in the apoptotic process and enhances cytokine production by DCs. In addition, preincubation of apoptotic cells with PTX3 enhances C1q binding and C3 deposition on the cell surface, suggesting a role for PTX3 in the complement-mediated clearance of apoptotic cells. Moreover, in the presence of dying cells, PTX3 restricts the cross presentation of antigens derived from dying cells. These results suggest that PTX3 has a dual role: protection against pathogens and control of autoimmunity.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000163661 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000027832 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Breviario F, d'Aniello EM, Golay J, Peri G, Bottazzi B, Bairoch A, Saccone S, Marzella R, Predazzi V, Rocchi M (November 1992). "Interleukin-1-inducible genes in endothelial cells. Cloning of a new gene related to C-reactive protein and serum amyloid P component". The Journal of Biological Chemistry. 267 (31): 22190–7. doi:10.1016/S0021-9258(18)41653-5. PMID 1429570.
6. "Entrez Gene: PTX3 Pentraxin-related gene, rapidly induced by IL-1 beta".
7. Emsley J, White HE, O'Hara BP, Oliva G, Srinivasan N, Tickle IJ, Blundell TL, Pepys MB, Wood SP (January 1994). "Structure of pentameric human serum amyloid P component". Nature. 367 (6461): 338–45. Bibcode:1994Natur.367..338E. doi:10.1038/367338a0. PMID 8114934. S2CID 4284282.
8. Wirestam L, Enocsson H, Skogh T, Eloranta ML, Rönnblom L, Sjöwall C, Wetterö J (July 2017). "Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro". Clinical and Experimental Immunology. 189 (1): 83–91. doi:10.1111/cei.12957. PMC 5461103. PMID 28257596.
9. ^ Garlanda C, Bottazzi B, Bastone A, Mantovani A (2005). "Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility". Annual Review of Immunology. 23: 337–66. doi:10.1146/annurev.immunol.23.021704.115756. PMID 15771574.
10. ^ Diniz SN, Nomizo R, Cisalpino PS, Teixeira MM, Brown GD, Mantovani A, Gordon S, Reis LF, Dias AA (April 2004). "PTX3 function as an opsonin for the dectin-1-dependent internalization of zymosan by macrophages". Journal of Leukocyte Biology. 75 (4): 649–56. doi:10.1189/jlb.0803371. PMID 14726497. S2CID 1172342.
11. ^ Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D'Ettorre C, Gianazza E, Tagliabue A, Salmona M, Tedesco F, Introna M, Mantovani A (December 1997). "Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component". The Journal of Biological Chemistry. 272 (52): 32817–23. doi:10.1074/jbc.272.52.32817. PMID 9407058.
12. ^ Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, Doni A, Vago L, Botto M, De Santis R, Carminati P, Siracusa G, Altruda F, Vecchi A, Romani L, Mantovani A (November 2002). "Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response". Nature. 420 (6912): 182–6. Bibcode:2002Natur.420..182G. doi:10.1038/nature01195. PMID 12432394. S2CID 4414588.
13. Nauta AJ, Bottazzi B, Mantovani A, Salvatori G, Kishore U, Schwaeble WJ, Gingras AR, Tzima S, Vivanco F, Egido J, Tijsma O, Hack EC, Daha MR, Roos A (February 2003). "Biochemical and functional characterization of the interaction between pentraxin 3 and C1q". European Journal of Immunology. 33 (2): 465–73. doi:10.1002/immu.200310022. PMID 12645945. S2CID 9479617.
14. Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, Doni A, Bastone A, Mantovani G, Beck Peccoz P, Salvatori G, Mahoney DJ, Day AJ, Siracusa G, Romani L, Mantovani A (April 2004). "PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in-vivo fertilization". Development. 131 (7): 1577–86. doi:10.1242/dev.01056. hdl:2434/758422. PMID 14998931.
15. Introna M, Alles VV, Castellano M, Picardi G, De Gioia L, Bottazzai B, Peri G, Breviario F, Salmona M, De Gregorio L, Dragani TA, Srinivasan N, Blundell TL, Hamilton TA, Mantovani A (March 1996). "Cloning of mouse ptx3, a new member of the pentraxin gene family expressed at extrahepatic sites". Blood. 87 (5): 1862–72. doi:10.1182/blood.V87.5.1862.1862. PMID 8634434.
16. Zatta M, Di Bella S, Bottazzi B, Rossi F, D'Agaro P, Segat L, et al. (December 2019). "Determination of pentraxin 3 levels in cerebrospinal fluid during central nervous system infections". European Journal of Clinical Microbiology & Infectious Diseases. 39 (4): 665–670. doi:10.1007/s10096-019-03767-w. hdl:11368/2972747. PMID 31813079. S2CID 208812200.
17. Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, Mantovani A (July 2001). "Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients". Critical Care Medicine. 29 (7): 1404–7. doi:10.1097/00003246-200107000-00017. PMID 11445697. S2CID 1709839.
18. Fazzini F, Peri G, Doni A, Dell'Antonio G, Dal Cin E, Bozzolo E, D'Auria F, Praderio L, Ciboddo G, Sabbadini MG, Manfredi AA, Mantovani A, Querini PR (December 2001). "PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation". Arthritis and Rheumatism. 44 (12): 2841–50. doi:10.1002/1529-0131(200112)44:12<2841::AID-ART472>3.0.CO;2-6. PMID 11762945.
19. Mairuhu AT, Peri G, Setiati TE, Hack CE, Koraka P, Soemantri A, Osterhaus AD, Brandjes DP, van der Meer JW, Mantovani A, van Gorp EC (August 2005). "Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections". Journal of Medical Virology. 76 (4): 547–52. doi:10.1002/jmv.20397. PMID 15977234. S2CID 24762210.
20. Azzurri A, Sow OY, Amedei A, Bah B, Diallo S, Peri G, Benagiano M, D'Elios MM, Mantovani A, Del Prete G (January 2005). "IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection". Microbes and Infection. 7 (1): 1–8. doi:10.1016/j.micinf.2004.09.004. PMID 15716076.
21. Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, Vago L, Pasqualini F, Signorini S, Soldateschi D, Tarli L, Schweiger C, Fresco C, Cecere R, Tognoni G, Mantovani A (October 2004). "Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction". Circulation. 110 (16): 2349–54. doi:10.1161/01.CIR.0000145167.30987.2E. PMID 15477419.
22. Gershov D, Kim S, Brot N, Elkon KB (November 2000). "C-Reactive protein binds to apoptotic cells, protects the cells from assembly of the terminal complement components, and sustains an antiinflammatory innate immune response: implications for systemic autoimmunity". The Journal of Experimental Medicine. 192 (9): 1353–64. doi:10.1084/jem.192.9.1353. PMC 2193350. PMID 11067883.
23. Familian A, Zwart B, Huisman HG, Rensink I, Roem D, Hordijk PL, Aarden LA, Hack CE (July 2001). "Chromatin-independent binding of serum amyloid P component to apoptotic cells". Journal of Immunology. 167 (2): 647–54. doi:10.4049/jimmunol.167.2.647. PMID 11441067.
24. ^ Rovere P, Peri G, Fazzini F, Bottazzi B, Doni A, Bondanza A, Zimmermann VS, Garlanda C, Fascio U, Sabbadini MG, Rugarli C, Mantovani A, Manfredi AA (December 2000). "The long pentraxin PTX3 binds to apoptotic cells and regulates their clearance by antigen-presenting dendritic cells". Blood. 96 (13): 4300–6. doi:10.1182/blood.V96.13.4300. PMID 11110705.
25. Baruah P, Propato A, Dumitriu IE, Rovere-Querini P, Russo V, Fontana R, Accapezzato D, Peri G, Mantovani A, Barnaba V, Manfredi AA (January 2006). "The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens". Blood. 107 (1): 151–8. doi:10.1182/blood-2005-03-1112. PMID 16166594.

Further reading

• Mantovani A, Garlanda C, Bottazzi B (June 2003). "Pentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity". Vaccine. 21 (Suppl 2): S43–7. doi:10.1016/S0264-410X(03)00199-3. PMID 12763682.
• He X, Han B, Liu M (May 2007). "Long pentraxin 3 in pulmonary infection and acute lung injury". American Journal of Physiology. Lung Cellular and Molecular Physiology. 292 (5): L1039–49. doi:10.1152/ajplung.00490.2006. PMID 17277044. S2CID 6386076.
• Lee TH, Wisniewski HG, Vilcek J (January 1992). "A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member of the family of hyaluronate binding proteins, closely related to the adhesion receptor CD44". The Journal of Cell Biology. 116 (2): 545–57. doi:10.1083/jcb.116.2.545. PMC 2289279. PMID 1730767.
• Lee GW, Goodman AR, Lee TH, Vilcek J (October 1994). "Relationship of TSG-14 protein to the pentraxin family of major acute phase proteins". Journal of Immunology. 153 (8): 3700–7. doi:10.4049/jimmunol.153.8.3700. PMID 7523502.
• Lee GW, Lee TH, Vilcek J (March 1993). "TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the pentaxin family of acute phase proteins". Journal of Immunology. 150 (5): 1804–12. doi:10.4049/jimmunol.150.5.1804. PMID 7679696.
• Alles VV, Bottazzi B, Peri G, Golay J, Introna M, Mantovani A (November 1994). "Inducible expression of PTX3, a new member of the pentraxin family, in human mononuclear phagocytes". Blood. 84 (10): 3483–93. doi:10.1182/blood.V84.10.3483.3483. PMID 7949102.
• Introna M, Breviario F, d'Aniello EM, Golay J, Dejana E, Mantovani A (December 1993). "IL-1 inducible genes in human umbilical vein endothelial cells". European Heart Journal. 14 Suppl K: 78–81. PMID 8131794.
• Vouret-Craviari V, Matteucci C, Peri G, Poli G, Introna M, Mantovani A (April 1997). "Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan". Infection and Immunity. 65 (4): 1345–50. doi:10.1128/IAI.65.4.1345-1350.1997. PMC 175138. PMID 9119472.
• Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D'Ettorre C, Gianazza E, Tagliabue A, Salmona M, Tedesco F, Introna M, Mantovani A (December 1997). "Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component". The Journal of Biological Chemistry. 272 (52): 32817–23. doi:10.1074/jbc.272.52.32817. PMID 9407058.
• Polentarutti N, Picardi G, Basile A, Cenzuales S, Rivolta A, Matteucci C, Peri G, Mantovani A, Introna M (February 1998). "Interferon-gamma inhibits expression of the long pentraxin PTX3 in human monocytes". European Journal of Immunology. 28 (2): 496–501. doi:10.1002/(SICI)1521-4141(199802)28:02<496::AID-IMMU496>3.0.CO;2-V. PMID 9521058. S2CID 84152144.
• Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, Pizzetti F, Maggioni AP, Moccetti T, Metra M, Cas LD, Ghezzi P, Sipe JD, Re G, Olivetti G, Mantovani A, Latini R (August 2000). "PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans". Circulation. 102 (6): 636–41. doi:10.1161/01.cir.102.6.636. PMID 10931803.
• Fazzini F, Peri G, Doni A, Dell'Antonio G, Dal Cin E, Bozzolo E, D'Auria F, Praderio L, Ciboddo G, Sabbadini MG, Manfredi AA, Mantovani A, Querini PR (December 2001). "PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation". Arthritis and Rheumatism. 44 (12): 2841–50. doi:10.1002/1529-0131(200112)44:12<2841::AID-ART472>3.0.CO;2-6. PMID 11762945.
• Klouche M, Brockmeyer N, Knabbe C, Rose-John S (May 2002). "Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in Kaposi's sarcoma cells". AIDS. 16 (8): F9–18. doi:10.1097/00002030-200205240-00001. PMID 12004288. S2CID 38550660.
• Napoleone E, Di Santo A, Bastone A, Peri G, Mantovani A, de Gaetano G, Donati MB, Lorenzet R (May 2002). "Long pentraxin PTX3 upregulates tissue factor expression in human endothelial cells: a novel link between vascular inflammation and clotting activation". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (5): 782–7. doi:10.1161/01.ATV.0000012282.39306.64. PMID 12006390.
• Rolph MS, Zimmer S, Bottazzi B, Garlanda C, Mantovani A, Hansson GK (May 2002). "Production of the long pentraxin PTX3 in advanced atherosclerotic plaques". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (5): e10–4. doi:10.1161/01.ATV.0000015595.95497.2F. PMID 12006411.
• Bussolati B, Peri G, Salvidio G, Verzola D, Mantovani A, Camussi G (February 2003). "The long pentraxin PTX3 is synthesized in IgA glomerulonephritis and activates mesangial cells". Journal of Immunology. 170 (3): 1466–72. doi:10.4049/jimmunol.170.3.1466. PMID 12538709.
• Abderrahim-Ferkoune A, Bezy O, Chiellini C, Maffei M, Grimaldi P, Bonino F, Moustaid-Moussa N, Pasqualini F, Mantovani A, Ailhaud G, Amri EZ (May 2003). "Characterization of the long pentraxin PTX3 as a TNFalpha-induced secreted protein of adipose cells". Journal of Lipid Research. 44 (5): 994–1000. doi:10.1194/jlr.M200382-JLR200. PMID 12611905.
• Nauta AJ, Bottazzi B, Mantovani A, Salvatori G, Kishore U, Schwaeble WJ, Gingras AR, Tzima S, Vivanco F, Egido J, Tijsma O, Hack EC, Daha MR, Roos A (February 2003). "Biochemical and functional characterization of the interaction between pentraxin 3 and C1q". European Journal of Immunology. 33 (2): 465–73. doi:10.1002/immu.200310022. PMID 12645945. S2CID 9479617.

• Genes on human chromosome 3