BioPAX pathway converted from "Defensins" in the Reactome database.DefensinsDefensinsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Pre-pro-defensins are cleaved to remove the signal peptidePre-pro-defensins are cleaved to remove the signal peptideThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97590901Golgi lumenGO0005796Pre-pro-defensins [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa23 [Golgi lumen]Defa42 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa40 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa5 [Golgi lumen]Defa17 [Golgi lumen]AY761185 [Golgi lumen]Defa36 [Golgi lumen]Defa-rs1 [Golgi lumen]Defb14 [Golgi lumen]Defa36 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa3 [Golgi lumen]Defa35 [Golgi lumen]Defa34 [Golgi lumen]Defa17 [Golgi lumen]Defb4 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa24 [Golgi lumen]Defa3 [Golgi lumen]Defa21 [Golgi lumen]Defa23 [Golgi lumen]Defa40 [Golgi lumen]Defa26 [Golgi lumen]Defa30 [Golgi lumen]Defa2 [Golgi lumen]Defa3 [Golgi lumen]Defa21 [Golgi lumen]Defa35 [Golgi lumen]Defa17 [Golgi lumen]Defa36 [Golgi lumen]Defa34 [Golgi lumen]Defa39 [Golgi lumen]Defa38 [Golgi lumen]Defa5 [Golgi lumen]Defa40 [Golgi lumen]Defa39 [Golgi lumen]Defa34 [Golgi lumen]Defa24 [Golgi lumen]Defa22 [Golgi lumen]Defa25 [Golgi lumen]AY761185 [Golgi lumen]Defb1 [Golgi lumen]Defa27 [Golgi lumen]Defa41 [Golgi lumen]AY761185 [Golgi lumen]Defa28 [Golgi lumen]Defa30 [Golgi lumen]Defa22 [Golgi lumen]Defa25 [Golgi lumen]Defa42 [Golgi lumen]Defa38 [Golgi lumen]Defa27 [Golgi lumen]Defa20 [Golgi lumen]Defa35 [Golgi lumen]Defa38 [Golgi lumen]Defa41 [Golgi lumen]Defa2 [Golgi lumen]Defa23 [Golgi lumen]Defa5 [Golgi lumen]Defa25 [Golgi lumen]Defa42 [Golgi lumen]Defa26 [Golgi lumen]Defa20 [Golgi lumen]Defa24 [Golgi lumen]Defa22 [Golgi lumen]Defa2 [Golgi lumen]Defa20 [Golgi lumen]Defa39 [Golgi lumen]Defa28 [Golgi lumen]Defa21 [Golgi lumen]Defa27 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa26 [Golgi lumen]Defa28 [Golgi lumen]Defa30 [Golgi lumen]Defa41 [Golgi lumen]Reactomehttp://www.reactome.orgMus musculusNCBI Taxonomy10090UniProtQ5G866UniProtD3YX03UniProtP17533UniProtL7N231UniProtP28312UniProtQ64016UniProtQ5ERI8UniProtK9J724UniProtQ7TNV9UniProtP50715UniProtP28310UniProtE9QLQ1UniProtD3Z0J0UniProtP82019UniProtQ5G865UniProtQ8C1P2UniProtQ3L180UniProtE9QPZ2UniProtP28309UniProtQ9D848UniProtQ5ERJ0UniProtQ8C1N8UniProtQ5G864UniProtP56386UniProtF2Z403UniProtD3YX02UniProtD3Z1V9UniProtQ45VN2Converted from EntitySet in ReactomeReactome DB_ID: 97592181Pro-defensins [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa34 [Golgi lumen]Defa39 [Golgi lumen]Defa17 [Golgi lumen]Defa28 [Golgi lumen]Defa34 [Golgi lumen]Defa40 [Golgi lumen]AY761185 [Golgi lumen]Defa42 [Golgi lumen]Defa-rs7 [Golgi lumen]Defb14 [Golgi lumen]Defb4 [Golgi lumen]Defa22 [Golgi lumen]Defa23 [Golgi lumen]Defa35 [Golgi lumen]Defa40 [Golgi lumen]Defa27 [Golgi lumen]Defa24 [Golgi lumen]Defa23 [Golgi lumen]Defa26 [Golgi lumen]Defa39 [Golgi lumen]Defb1 [Golgi lumen]Defa39 [Golgi lumen]Defa38 [Golgi lumen]Defa3 [Golgi lumen]Defa2 [Golgi lumen]Defa26 [Golgi lumen]Defa41 [Golgi lumen]Defa20 [Golgi lumen]Defa30 [Golgi lumen]Defa24 [Golgi lumen]Defa36 [Golgi lumen]Defa20 [Golgi lumen]Defa21 [Golgi lumen]Defa5 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa42 [Golgi lumen]Defa22 [Golgi lumen]AY761185 [Golgi lumen]Defa21 [Golgi lumen]AY761185 [Golgi lumen]Defa38 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa25 [Golgi lumen]Defa25 [Golgi lumen]Defa38 [Golgi lumen]Defa20 [Golgi lumen]Defa17 [Golgi lumen]Defa35 [Golgi lumen]Defa34 [Golgi lumen]Defa26 [Golgi lumen]Defa24 [Golgi lumen]Defa27 [Golgi lumen]Defa36 [Golgi lumen]Defa25 [Golgi lumen]Defa3 [Golgi lumen]Defa5 [Golgi lumen]Defa3 [Golgi lumen]Defa28 [Golgi lumen]Defa30 [Golgi lumen]Defa40 [Golgi lumen]Defa17 [Golgi lumen]Defa27 [Golgi lumen]Defa23 [Golgi lumen]Defa41 [Golgi lumen]Defa2 [Golgi lumen]Defa5 [Golgi lumen]Defa28 [Golgi lumen]Defa36 [Golgi lumen]Defa22 [Golgi lumen]Defa2 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa21 [Golgi lumen]Defa42 [Golgi lumen]Defa35 [Golgi lumen]Defa30 [Golgi lumen]Defa41 [Golgi lumen]Defa-rs7 [Golgi lumen]Reactome Database ID Release 759759220Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759220ReactomeR-MMU-14620231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462023.1Pre-pro-defensins are cleaved in the golgi by undefined proteases which remove the signal peptide (Yang et al. 2004, Pazgier et al. 2006). Subsequently, alpha-defensins are cleaved again to produce the biologically active mature peptide. Beta defensins have much shorter propieces and may be active once the signal peptide is removed. Further N-terminal processing of the mature defensin may yield multiple forms of the same peptide (Pazgier et al. 2006). 15032578Pubmed2004Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defenseYang, DBiragyn, AHoover, DMLubkowski, JOppenheim, JJAnnu Rev Immunol 22:181-21512949495Pubmed2003Defensins: antimicrobial peptides of innate immunityGanz, TNat Rev Immunol 3:710-2016710608Pubmed2006Human beta-defensinsPazgier, MHoover, DMYang, DLu, WLubkowski, JCell Mol Life Sci 63:1294-313inferred by electronic annotationIEAGOIEAAlpha-defensinsAlpha-defensinsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Pro-HNP1-4 are cleaved to biologically active defensinPro-HNP1-4 are cleaved to biologically active defensinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97592221Pro-defensins alpha 1-4 [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa25 [Golgi lumen]Defa38 [Golgi lumen]Defa17 [Golgi lumen]Defa35 [Golgi lumen]Defa34 [Golgi lumen]Defa40 [Golgi lumen]AY761185 [Golgi lumen]Defa42 [Golgi lumen]Defa24 [Golgi lumen]Defa36 [Golgi lumen]Defa22 [Golgi lumen]Defa3 [Golgi lumen]Defa27 [Golgi lumen]Defa23 [Golgi lumen]Defa26 [Golgi lumen]Defa39 [Golgi lumen]Defa41 [Golgi lumen]Defa20 [Golgi lumen]Defa2 [Golgi lumen]Defa28 [Golgi lumen]Defa5 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa21 [Golgi lumen]Defa30 [Golgi lumen]Defa-rs7 [Golgi lumen]Converted from EntitySet in ReactomeReactome DB_ID: 97587181Defensins alpha 1-4 [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa26 [Golgi lumen]Defa39 [Golgi lumen]Defa23 [Golgi lumen]Defa25 [Golgi lumen]Defa41 [Golgi lumen]AY761185 [Golgi lumen]Defa35 [Golgi lumen]Defa21 [Golgi lumen]Defa24 [Golgi lumen]Defa24 [Golgi lumen]Defa2 [Golgi lumen]Defa41 [Golgi lumen]Defa2 [Golgi lumen]Defa34 [Golgi lumen]Defa28 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa23 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa28 [Golgi lumen]Defa40 [Golgi lumen]Defa22 [Golgi lumen]Defa40 [Golgi lumen]Defa35 [Golgi lumen]Defa36 [Golgi lumen]Defa3 [Golgi lumen]Defa26 [Golgi lumen]Defa34 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa38 [Golgi lumen]Defa17 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa30 [Golgi lumen]AY761185 [Golgi lumen]Defa21 [Golgi lumen]Defa42 [Golgi lumen]Defa27 [Golgi lumen]Defa20 [Golgi lumen]Defa5 [Golgi lumen]Defa30 [Golgi lumen]Defa25 [Golgi lumen]Defa3 [Golgi lumen]Defa22 [Golgi lumen]Defa27 [Golgi lumen]Defa39 [Golgi lumen]Defa20 [Golgi lumen]Defa38 [Golgi lumen]Defa36 [Golgi lumen]Defa42 [Golgi lumen]Defa17 [Golgi lumen]Defa5 [Golgi lumen]Converted from EntitySet in ReactomeReactome DB_ID: 97593801Pro-defensin fragments [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa17 [Golgi lumen]Defa21 [Golgi lumen]Defa22 [Golgi lumen]Defa42 [Golgi lumen]Defa34 [Golgi lumen]Defa39 [Golgi lumen]Defa5 [Golgi lumen]Defa38 [Golgi lumen]Defa28 [Golgi lumen]Defa30 [Golgi lumen]Defa25 [Golgi lumen]Defa27 [Golgi lumen]Defa3 [Golgi lumen]Defa40 [Golgi lumen]Defa26 [Golgi lumen]Defa20 [Golgi lumen]Defa3 [Golgi lumen]Defa39 [Golgi lumen]Defa2 [Golgi lumen]AY761185 [Golgi lumen]Defa42 [Golgi lumen]Defa34 [Golgi lumen]Defa23 [Golgi lumen]Defa36 [Golgi lumen]Defa41 [Golgi lumen]Defa24 [Golgi lumen]Defa40 [Golgi lumen]Defa2 [Golgi lumen]Defa35 [Golgi lumen]Defa35 [Golgi lumen]Defa20 [Golgi lumen]Defa23 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa21 [Golgi lumen]Defa5 [Golgi lumen]Defa30 [Golgi lumen]Defa17 [Golgi lumen]Defa41 [Golgi lumen]Defa27 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa22 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa38 [Golgi lumen]Defa36 [Golgi lumen]Defa25 [Golgi lumen]Defa-rs7 [Golgi lumen]Defa24 [Golgi lumen]Defa28 [Golgi lumen]Defa26 [Golgi lumen]AY761185 [Golgi lumen]Reactome Database ID Release 759759382Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759382ReactomeR-MMU-14620391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462039.1Synthesis of alpha defensins takes place in neutrophil precursor cells, the promyelocytes, in the bone marrow. Pro HNP1-4 are cleaved in the Golgi body, with HNP-2 being derived from cleavage of the N-terminal amino acid from HNP-1 or HNP-3. The defensin propiece is not only important for correct sub-cellular trafficking and sorting but also inhibits HNP activity (Valore et al. 1996, Wu et al. 2007). The resulting mature peptides are sorted to primary neutrophil (azurophil) granules for storage (Valore & Ganz 1992, Harwig et al. 1992, Cowland & Borregaard).17355880Pubmed2007Impact of pro segments on the folding and function of human neutrophil alpha-defensinsWu, ZLi, XEricksen, Bde Leeuw, EZou, GZeng, PXie, CLi, CLubkowski, JLu, WYLu, WJ Mol Biol 368:537-4910614782Pubmed1999The individual regulation of granule protein mRNA levels during neutrophil maturation explains the heterogeneity of neutrophil granulesCowland, JBBorregaard, NJ Leukoc Biol 66:989-951547345Pubmed1992Characterization of defensin precursors in mature human neutrophilsHarwig, SSPark, ASLehrer, RIBlood 79:1532-71339298Pubmed1992Posttranslational processing of defensins in immature human myeloid cellsValore, EVGanz, TBlood 79:1538-44inferred by electronic annotationIEAGOIEAHNP1-4 are stored in primary neutrophil granulesHNP1-4 are stored in primary neutrophil granulesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97587181Converted from EntitySet in ReactomeReactome DB_ID: 97588761azurophil granule lumenGO0035578Defensins alpha 1-4 [azurophil granule lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa39 [azurophil granule lumen]Defa23 [azurophil granule lumen]Defa40 [azurophil granule lumen]Defa42 [azurophil granule lumen]Defa22 [azurophil granule lumen]Defa-rs1 [azurophil granule lumen]Defa24 [azurophil granule lumen]Defa22 [azurophil granule lumen]Defa30 [azurophil granule lumen]Defa3 [azurophil granule lumen]Defa17 [azurophil granule lumen]Defa-rs7 [azurophil granule lumen]Defa20 [azurophil granule lumen]Defa2 [azurophil granule lumen]AY761185 [azurophil granule lumen]Defa28 [azurophil granule lumen]Defa34 [azurophil granule lumen]Defa5 [azurophil granule lumen]AY761185 [azurophil granule lumen]Defa27 [azurophil granule lumen]Defa21 [azurophil granule lumen]Defa38 [azurophil granule lumen]Defa35 [azurophil granule lumen]Defa-rs1 [azurophil granule lumen]Defa42 [azurophil granule lumen]Defa24 [azurophil granule lumen]Defa28 [azurophil granule lumen]Defa25 [azurophil granule lumen]Defa40 [azurophil granule lumen]Defa27 [azurophil granule lumen]Defa23 [azurophil granule lumen]Defa41 [azurophil granule lumen]Defa39 [azurophil granule lumen]Defa36 [azurophil granule lumen]Defa21 [azurophil granule lumen]Defa30 [azurophil granule lumen]Defa25 [azurophil granule lumen]Defa41 [azurophil granule lumen]Defa36 [azurophil granule lumen]Defa3 [azurophil granule lumen]Defa38 [azurophil granule lumen]Defa-rs7 [azurophil granule lumen]Defa20 [azurophil granule lumen]Defa2 [azurophil granule lumen]Defa34 [azurophil granule lumen]Defa35 [azurophil granule lumen]Defa26 [azurophil granule lumen]Defa17 [azurophil granule lumen]Defa5 [azurophil granule lumen]Defa26 [azurophil granule lumen]Reactome Database ID Release 759758878Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758878ReactomeR-MMU-14620031Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462003.1Alpha defensins HNP1-4, the neutrophil defensins, are stored in biologically active form in neutrophil primary (azurophil) granules, where they make up 5-10% of total cellular protein in these cells (Lehrere et al. 1993). The relative amounts of peptide for HNP-1 to -3 are 2:2:1 with HNP-4 being only a minor component.2997278Pubmed1985Defensins. Natural peptide antibiotics of human neutrophilsGanz, TSelsted, MESzklarek, DHarwig, SSDaher, KBainton, DFLehrer, RIJ Clin Invest 76:1427-352500436Pubmed1989Purification and characterization of human neutrophil peptide 4, a novel member of the defensin familyWilde, CGGriffith, JEMarra, MNSnable, JLScott, RWJ Biol Chem 264:11200-38476558Pubmed1993Defensins: antimicrobial and cytotoxic peptides of mammalian cellsLehrer, RILichtenstein, AKGanz, TAnnu Rev Immunol 11:105-28inferred by electronic annotationIEAGOIEAHNP1-4 are released into phagocytic vacuolesHNP1-4 are released into phagocytic vacuolesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97588761Converted from EntitySet in ReactomeReactome DB_ID: 97593841extracellular regionGO0005576Defensins alpha 1-4 [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa34 [extracellular region]Defa20 [extracellular region]Defa41 [extracellular region]Defa3 [extracellular region]Defa21 [extracellular region]Defa24 [extracellular region]Defa26 [extracellular region]Defa28 [extracellular region]Defa23 [extracellular region]AY761185 [extracellular region]Defa39 [extracellular region]Defa41 [extracellular region]Defa22 [extracellular region]Defa25 [extracellular region]Defa17 [extracellular region]Defa24 [extracellular region]Defa39 [extracellular region]Defa-rs1 [extracellular region]Defa30 [extracellular region]Defa5 [extracellular region]Defa5 [extracellular region]Defa28 [extracellular region]Defa30 [extracellular region]Defa38 [extracellular region]Defa-rs1 [extracellular region]Defa40 [extracellular region]Defa21 [extracellular region]Defa2 [extracellular region]Defa25 [extracellular region]Defa23 [extracellular region]Defa42 [extracellular region]Defa3 [extracellular region]Defa17 [extracellular region]Defa27 [extracellular region]Defa2 [extracellular region]Defa27 [extracellular region]Defa22 [extracellular region]Defa-rs7 [extracellular region]Defa38 [extracellular region]Defa40 [extracellular region]Defa42 [extracellular region]Defa-rs7 [extracellular region]AY761185 [extracellular region]Defa35 [extracellular region]Defa36 [extracellular region]Defa20 [extracellular region]Defa35 [extracellular region]Defa36 [extracellular region]Defa34 [extracellular region]Defa26 [extracellular region]Reactome Database ID Release 759759386Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759386ReactomeR-MMU-14620411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462041.1Human neutrophils contain thousands of cytoplasmic granules. These membrane-bound organelles act as storage compartments destined for secretion or in the case of azurophil granules, destined for fusion with phagosomes. A small amount of defensin, but perhaps not enough for antimicrobial activity, may be released extracellularly by neutrophils (Ganz 1987).10618521Pubmed1999Processing and targeting of granule proteins in human neutrophilsGullberg, UBengtsson, NBülow, EGarwicz, DLindmark, AOlsson, IJ Immunol Methods 232:201-103643886Pubmed1987Extracellular release of antimicrobial defensins by human polymorphonuclear leukocytesGanz, TInfect Immun 55:568-718329717Pubmed1993Posttranslational processing and targeting of transgenic human defensin in murine granulocyte, macrophage, fibroblast, and pituitary adenoma cell linesGanz, TLiu, LValore, EVOren, ABlood 82:641-501302183Pubmed1992Defensins: endogenous antibiotic peptides from human leukocytesLehrer, RIGanz, TCiba Found Symp 171:276-90; discussion 290-3inferred by electronic annotationIEAGOIEApro-defensin alpha 5 is stored in Paneth cell granulespro-defensin alpha 5 is stored in Paneth cell granulesThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97585061Homologues of DEFA5(20-94) [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa25 [Golgi lumen]Defa38 [Golgi lumen]Defa17 [Golgi lumen]Defa35 [Golgi lumen]Defa34 [Golgi lumen]Defa40 [Golgi lumen]AY761185 [Golgi lumen]Defa42 [Golgi lumen]Defa24 [Golgi lumen]Defa36 [Golgi lumen]Defa22 [Golgi lumen]Defa3 [Golgi lumen]Defa27 [Golgi lumen]Defa23 [Golgi lumen]Defa26 [Golgi lumen]Defa39 [Golgi lumen]Defa41 [Golgi lumen]Defa20 [Golgi lumen]Defa2 [Golgi lumen]Defa28 [Golgi lumen]Defa5 [Golgi lumen]Defa-rs1 [Golgi lumen]Defa21 [Golgi lumen]Defa30 [Golgi lumen]Defa-rs7 [Golgi lumen]Converted from EntitySet in ReactomeReactome DB_ID: 97585581secretory granule lumenGO0034774Homologues of DEFA5(20-94) [secretory granule lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa24 [secretory granule lumen]Defa5 [secretory granule lumen]Defa20 [secretory granule lumen]Defa17 [secretory granule lumen]Defa21 [secretory granule lumen]Defa42 [secretory granule lumen]Defa-rs1 [secretory granule lumen]Defa40 [secretory granule lumen]Defa23 [secretory granule lumen]Defa38 [secretory granule lumen]Defa36 [secretory granule lumen]Defa39 [secretory granule lumen]Defa27 [secretory granule lumen]Defa26 [secretory granule lumen]Defa35 [secretory granule lumen]Defa22 [secretory granule lumen]Defa28 [secretory granule lumen]Defa30 [secretory granule lumen]Defa3 [secretory granule lumen]Defa34 [secretory granule lumen]Defa25 [secretory granule lumen]Defa2 [secretory granule lumen]AY761185 [secretory granule lumen]Defa41 [secretory granule lumen]Defa-rs7 [secretory granule lumen]Reactome Database ID Release 759758560Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758560ReactomeR-MMU-14619951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461995.1Pro-defensin alpha 5 is stored in the granules of Paneth cells in the small intestine (Porter et al. 1997). This pro-peptide has some antimicrobial activity but is not as effective as the mature peptide (Ghosh et al. 2002).12021776Pubmed2002Paneth cell trypsin is the processing enzyme for human defensin-5Ghosh, DPorter, EShen, BLee, SKWilk, DDrazba, JYadav, SPCrabb, JWGanz, TBevins, CLNat Immunol 3:583-909169779Pubmed1997Localization of human intestinal defensin 5 in Paneth cell granulesPorter, EMLiu, LOren, AAnton, PAGanz, TInfect Immun 65:2389-95inferred by electronic annotationIEAGOIEApro-defensin alpha 5 is secretedpro-defensin alpha 5 is secretedThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97585581Converted from EntitySet in ReactomeReactome DB_ID: 97584311Homologues of DEFA5(20-94) [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa3 [extracellular region]Defa21 [extracellular region]Defa39 [extracellular region]Defa23 [extracellular region]Defa17 [extracellular region]Defa-rs1 [extracellular region]Defa28 [extracellular region]Defa-rs7 [extracellular region]Defa20 [extracellular region]Defa5 [extracellular region]Defa34 [extracellular region]Defa35 [extracellular region]Defa40 [extracellular region]Defa30 [extracellular region]Defa36 [extracellular region]Defa22 [extracellular region]Defa42 [extracellular region]Defa2 [extracellular region]Defa25 [extracellular region]Defa41 [extracellular region]Defa24 [extracellular region]Defa26 [extracellular region]Defa27 [extracellular region]AY761185 [extracellular region]Defa38 [extracellular region]Reactome Database ID Release 759758880Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758880ReactomeR-MMU-14620051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462005.1Pro defensin alpha 5 is secreted from the storage granules of Paneth cells in the small intestine (Porter et al. 1997).inferred by electronic annotationIEAGOIEApro-HD5 is cleaved by trypsinpro-HD5 is cleaved by trypsinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97584311Converted from EntitySet in ReactomeReactome DB_ID: 97583131Homologues of DEFA5(?-94) [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa30 [extracellular region]AY761185 [extracellular region]Defa41 [extracellular region]Defa5 [extracellular region]Defa27 [extracellular region]Defa28 [extracellular region]Defa38 [extracellular region]Defa-rs1 [extracellular region]Defa17 [extracellular region]Defa2 [extracellular region]Defa25 [extracellular region]Defa26 [extracellular region]Defa20 [extracellular region]Defa39 [extracellular region]Defa35 [extracellular region]Defa-rs7 [extracellular region]Defa24 [extracellular region]Defa34 [extracellular region]Defa23 [extracellular region]Defa40 [extracellular region]Defa36 [extracellular region]Defa42 [extracellular region]Defa3 [extracellular region]Defa21 [extracellular region]Defa22 [extracellular region]PHYSIOL-LEFT-TO-RIGHTACTIVATIONConverted from EntitySet in ReactomeReactome DB_ID: 9758451Trypsin 2, 3 [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityGm5771 [extracellular region]Prss1 [extracellular region]Try5 [extracellular region]Try10 [extracellular region]Try4 [extracellular region]Gm10334 [extracellular region]Gm5771 [extracellular region]Try4 [extracellular region]Try10 [extracellular region]Try5 [extracellular region]Gm10334 [extracellular region]Prss3 [extracellular region]Prss2 [extracellular region]Prss3 [extracellular region]Prss2 [extracellular region]Prss1 [extracellular region]UniProtQ792Y9UniProtQ9Z1R9UniProtQ9QUK9UniProtQ792Z1UniProtQ9R0T7UniProtQ792Y8UniProtQ792Z0UniProtP07146GO0008236GO molecular functionReactome Database ID Release 759758452Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758452Reactome Database ID Release 759758454Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758454ReactomeR-MMU-14619931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461993.1Pro HD5 is stored and secreted from granules of Paneth cells in the small intestine (Porter et al. 1997, Cunliffe et al. 2001). The serine protease tryspin colocalizes to these granules as the inactive zymogen trypsinogen. Removal of the defensin propiece occurs extracellularly after release in to the crypt lumen, and is mediated by trypsin 2 (anionic trypsin) and/or trypsin-3 (mesotrypsin) which are converted to their active forms by enteroprotease like enzymes or by autoactivation (Ghosh et al. 2002, Ouelette 2011). 11156637Pubmed2001Human defensin 5 is stored in precursor form in normal Paneth cells and is expressed by some villous epithelial cells and by metaplastic Paneth cells in the colon in inflammatory bowel diseaseCunliffe, RNRose, FRKeyte, JAbberley, LChan, WCMahida, YRGut 48:176-8521560070Pubmed2011Paneth cell ?-defensins in enteric innate immunityOuellette, AJCell Mol Life Sci 68:2215-29inferred by electronic annotationIEAGOIEAAlpha-defensins form biologically active dimersAlpha-defensins form biologically active dimersThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97588822Alpha-defensins [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa5 [extracellular region]Defa27 [extracellular region]Defa30 [extracellular region]Defa-rs1 [extracellular region]Defa28 [extracellular region]Defa24 [extracellular region]Defa24 [extracellular region]Defa17 [extracellular region]Defa23 [extracellular region]Defa26 [extracellular region]Defa23 [extracellular region]Defa39 [extracellular region]Defa39 [extracellular region]Defa22 [extracellular region]Defa23 [extracellular region]Defa22 [extracellular region]Defa34 [extracellular region]Defa23 [extracellular region]Defa2 [extracellular region]Defa34 [extracellular region]Defa17 [extracellular region]Defa24 [extracellular region]Defa39 [extracellular region]Defa-rs7 [extracellular region]Defa-rs1 [extracellular region]Defa25 [extracellular region]Defa3 [extracellular region]AY761185 [extracellular region]Defa5 [extracellular region]Defa35 [extracellular region]Defa21 [extracellular region]Defa5 [extracellular region]Defa30 [extracellular region]Defa41 [extracellular region]Defa5 [extracellular region]Defa30 [extracellular region]Defa38 [extracellular region]Defa38 [extracellular region]Defa2 [extracellular region]Defa3 [extracellular region]Defa25 [extracellular region]Defa21 [extracellular region]Defa25 [extracellular region]Defa42 [extracellular region]Defa20 [extracellular region]Defa-rs7 [extracellular region]Defa17 [extracellular region]Defa24 [extracellular region]Defa2 [extracellular region]Defa-rs1 [extracellular region]Defa22 [extracellular region]Defa-rs7 [extracellular region]Defa38 [extracellular region]Defa40 [extracellular region]AY761185 [extracellular region]Defa42 [extracellular region]Defa38 [extracellular region]Defa36 [extracellular region]Defa-rs7 [extracellular region]Defa25 [extracellular region]Defa41 [extracellular region]Defa42 [extracellular region]Defa36 [extracellular region]Defa28 [extracellular region]Defa36 [extracellular region]Defa42 [extracellular region]Defa34 [extracellular region]Defa34 [extracellular region]Defa20 [extracellular region]Defa41 [extracellular region]Defa3 [extracellular region]Defa21 [extracellular region]Defa-rs1 [extracellular region]Defa26 [extracellular region]Defa24 [extracellular region]Defa2 [extracellular region]Defa28 [extracellular region]Defa17 [extracellular region]AY761185 [extracellular region]Defa35 [extracellular region]Defa35 [extracellular region]Defa21 [extracellular region]Defa38 [extracellular region]Defa41 [extracellular region]Defa41 [extracellular region]Defa25 [extracellular region]Defa28 [extracellular region]Defa36 [extracellular region]Defa42 [extracellular region]Defa17 [extracellular region]Defa26 [extracellular region]Defa30 [extracellular region]Defa39 [extracellular region]Defa3 [extracellular region]Defa22 [extracellular region]Defa40 [extracellular region]Defa27 [extracellular region]Defa36 [extracellular region]AY761185 [extracellular region]Defa28 [extracellular region]Defa-rs1 [extracellular region]Defa40 [extracellular region]Defa21 [extracellular region]Defa26 [extracellular region]Defa23 [extracellular region]Defa5 [extracellular region]Defa20 [extracellular region]Defa39 [extracellular region]Defa3 [extracellular region]Defa40 [extracellular region]Defa27 [extracellular region]Defa22 [extracellular region]Defa27 [extracellular region]Defa30 [extracellular region]Defa-rs7 [extracellular region]AY761185 [extracellular region]Defa40 [extracellular region]Defa35 [extracellular region]Defa20 [extracellular region]Defa27 [extracellular region]Defa35 [extracellular region]Defa2 [extracellular region]Defa34 [extracellular region]Defa26 [extracellular region]Defa20 [extracellular region]Converted from EntitySet in ReactomeReactome DB_ID: 97583711Alpha-defensin dimers [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 759758884Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758884ReactomeR-MMU-14620141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462014.1The crystal structure of human alpha-defensin HNP-3 revealed that it forms a dimer containing a six-stranded beta-sheet region (Hill et al. 1991). NMR studies indicate that HNP-1 can also form dimers or higher-order aggregates in solution and artificial lipid bilayers (Zhang et al. 1992, 2010a, 2010b). Models of alpha and beta defensins suggest that dimerization and/or higher order structures are characteristic, though not univeral or required for the biological effects of some beta-defensins (Suresh & Verma 2006, Pazgier et al. 2006).1445872Pubmed1992NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1Zhang, XLSelsted, MEPardi, ABiochemistry 31:11348-5617088326Pubmed2006Crystal structures of human alpha-defensins HNP4, HD5, and HD6Szyk, AWu, ZTucker, KYang, DLu, WLubkowski, JProtein Sci 15:2749-6020097206Pubmed2010Resonance assignment and three-dimensional structure determination of a human alpha-defensin, HNP-1, by solid-state NMRZhang, YDoherty, TLi, JLu, WBarinka, CLubkowski, JHong, MJ Mol Biol 397:408-2220961099Pubmed2010The membrane-bound structure and topology of a human ?-defensin indicate a dimer pore mechanism for membrane disruptionZhang, YLu, WHong, MBiochemistry 49:9770-8217254301Pubmed2006Modelling study of dimerization in mammalian defensinsSuresh, AVerma, CBMC Bioinformatics 7:S172006422Pubmed1991Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of membrane permeabilizationHill, CPYee, JSelsted, MEEisenberg, DScience 251:1481-5inferred by electronic annotationIEAGOIEAAlpha-defensin dimers adsorb onto microbial membrane anionic phospholipidsAlpha-defensin dimers adsorb onto microbial membrane anionic phospholipidsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97583711Reactome DB_ID: 14620491plasma membraneGO0005886anionic phospholipid [ChEBI:62643]anionic phospholipidphospholipid anionanionic phospholipidsphospholipid anionsChEBI62643Reactome DB_ID: 97583731Alpha-defensin dimers:anionic phospholipids [plasma membrane]Alpha-defensin dimers:anionic phospholipidsConverted from EntitySet in ReactomeReactome DB_ID: 97583711Reactome DB_ID: 14620491Reactome Database ID Release 759758373Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758373ReactomeR-MMU-14713451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471345.1Reactome Database ID Release 759758375Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758375ReactomeR-MMU-14619711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461971.1The alpha-defensin dimers adsorb onto microbial membrane anionic phospholipids, represented here as a complex of alpha-defensin dimers and a representative set of phospholipid molecules 'membrane anionic phospholipids'. The polar topology of defensins, with their spatially separated charged and hydrophobic regions, allows them to insert into microbial cell membranes, which contains more negatively charged phospholipids than mammalian cell membranes (Lohner et al. 1997). Defensins permeabilize membrane vesicles (Lehrer et al. 1989) with a greater effect on vesicles rich in negatively charged phospholipids (Fuji et al. 1993, Wimley et al. 1994).9063901Pubmed1997Differential scanning microcalorimetry indicates that human defensin, HNP-2, interacts specifically with biomembrane mimetic systemsLohner, KLatal, ALehrer, RIGanz, TBiochemistry 36:1525-318401215Pubmed1993Defensins promote fusion and lysis of negatively charged membranesFujii, GSelsted, MEEisenberg, DProtein Sci 2:1301-122668334Pubmed1989Interaction of human defensins with Escherichia coli. Mechanism of bactericidal activityLehrer, RIBarton, ADaher, KAHarwig, SSGanz, TSelsted, MEJ Clin Invest 84:553-617833799Pubmed1994Interactions between human defensins and lipid bilayers: evidence for formation of multimeric poresWimley, WCSelsted, MEWhite, SHProtein Sci 3:1362-7318973303Pubmed2008Mechanisms of alpha-defensin bactericidal action: comparative membrane disruption by Cryptdin-4 and its disulfide-null analogueHadjicharalambous, CSheynis, TJelinek, RShanahan, MTOuellette, AJGizeli, EBiochemistry 47:12626-34inferred by electronic annotationIEAGOIEAAlpha-defensin dimers multimerize to form a pore complexAlpha-defensin dimers multimerize to form a pore complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97583736Reactome DB_ID: 97583771Alpha-defensin pore complex [plasma membrane]Alpha-defensin pore complexReactome DB_ID: 97583736Reactome Database ID Release 759758377Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758377ReactomeR-MMU-14713551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471355.1Reactome Database ID Release 759758379Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9758379ReactomeR-MMU-14619821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461982.1Once adsorbed/inserted into the membrane, alpha defensins are believed to aggregate into pore forming structures. Based on vesicle leakage and dextran permeability experiments, Wimley et al. (1994) proposed a multimeric pore model consisting of 6-8 defensin dimers which come together to form a large pore with inner diameter of 2-2.5nm. More recently using solid-state NMR and artificial lipid bilayers, Zhang et al. (2010) provide evidence of a dimer pore model in which the polar top of the dimer lines an aqueous pore while the hydrophobic bottom faces the lipid chains. Regardless of the exact conformation, the resulting pores then allow the efflux of essential microbial cell components.inferred by electronic annotationIEAGOIEAHNP1-3 bind CD4HNP1-3 bind CD4This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97593841Reactome DB_ID: 97277811UniProt:P06332Cd4UniProtP06332Chain Coordinates26EQUAL458EQUALReactome DB_ID: 97594661Defensins alpha 1-3:CD4 [plasma membrane]Defensins alpha 1-3:CD4Converted from EntitySet in ReactomeReactome DB_ID: 97593841Reactome DB_ID: 9727781126EQUAL458EQUALReactome Database ID Release 759759466Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759466ReactomeR-MMU-14713521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471352.1Reactome Database ID Release 759759468Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759468ReactomeR-MMU-14713141Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471314.1Alpha-defensins, theta-defensins and their synthetic analogues the retrocyclins have been shown in numerous studies to have anti-HIV-1 activity (Chang & Klotman 2004). This appears to be mediated via multiple mechanisms including direct viral inactivation and down regulation of host-cell target co-receptors important for viral entry (Furci et al. 2007, Seidel et al. 2010). Further, HNPs 1 3, act as lectins and bind with relatively high affinity to gp120 (KD range, 15.8-52.8 nM) on the HIV-1 envelope and CD4 (KD range, 8.0-34.9 nM) on host target cells, both important molecules for viral entry (Wang et al. 2004). Artificial theta defensins, the retrocyclins, predicted from the human pseudogenes bind with even higher affinity whereas HNP-4 binding is much weaker (Wu et al. 2005). Alpha defensins have been demonstrated to inhibit the binding of gp120 to CD4 thus blocking HIV-1 fusion with its target cells (Furci et al. 2007).17132727Pubmed2007Alpha-defensins block the early steps of HIV-1 infection: interference with the binding of gp120 to CD4Furci, LSironi, FTolazzi, MVassena, LLusso, PBlood 109:2928-3520305815Pubmed2010Cyclic and acyclic defensins inhibit human immunodeficiency virus type-1 replication by different mechanismsSeidel, AYe, Yde Armas, LRSoto, MYarosh, WMarcsisin, RATran, DSelsted, MECamerini, DPLoS One 5:e973719024344Pubmed2008Neutrophil-derived defensins as modulators of innate immune functionRehaume, LMHancock, RECrit Rev Immunol 28:185-20015210812Pubmed2004Activity of alpha- and theta-defensins against primary isolates of HIV-1Wang, WOwen, SMRudolph, DLCole, AMHong, TWaring, AJLal, RBLehrer, RIJ Immunol 173:515-2015595433Pubmed2004Defensins: natural anti-HIV peptidesChang, TLKlotman, MEAIDS Rev 6:161-8inferred by electronic annotationIEAGOIEA2.4.2.31ADP-Ribosylation of HNP-1ADP-Ribosylation of HNP-1This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97581511Homologues of DEFA1(65-94) [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa34 [extracellular region]Defa28 [extracellular region]Defa20 [extracellular region]Defa-rs1 [extracellular region]Defa40 [extracellular region]Defa21 [extracellular region]Defa2 [extracellular region]Defa24 [extracellular region]Defa25 [extracellular region]Defa23 [extracellular region]Defa42 [extracellular region]AY761185 [extracellular region]Defa3 [extracellular region]Defa39 [extracellular region]Defa17 [extracellular region]Defa27 [extracellular region]Defa41 [extracellular region]Defa22 [extracellular region]Defa-rs7 [extracellular region]Defa38 [extracellular region]Defa35 [extracellular region]Defa36 [extracellular region]Defa30 [extracellular region]Defa5 [extracellular region]Defa26 [extracellular region]Converted from EntitySet in ReactomeReactome DB_ID: 97646551Homologues of omega-N-(ADP-ribosyl)-L-arginine-DEFA1(65-94) [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefa30 [extracellular region]Defa40 [extracellular region]Defa2 [extracellular region]Defa22 [extracellular region]Defa42 [extracellular region]Defa-rs7 [extracellular region]Defa28 [extracellular region]Defa26 [extracellular region]Defa25 [extracellular region]Defa36 [extracellular region]AY761185 [extracellular region]Defa39 [extracellular region]Defa21 [extracellular region]Defa5 [extracellular region]Defa-rs1 [extracellular region]Defa17 [extracellular region]Defa27 [extracellular region]Defa34 [extracellular region]Defa20 [extracellular region]Defa3 [extracellular region]Defa24 [extracellular region]Defa38 [extracellular region]Defa23 [extracellular region]Defa41 [extracellular region]Defa35 [extracellular region]PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 9764659UniProt:Q60935Art1UniProtQ6093523EQUAL295EQUALGO0003956GO molecular functionReactome Database ID Release 759764660Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764660Reactome Database ID Release 759764662Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764662ReactomeR-MMU-19723851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1972385.1HNP-1 is recognized as a substrate by arginine-specific ADP-ribosyltransferase-1 which ribosylates Arg-14 of the peptide. The modified defensin has reduced antimicrobial and cytotoxic activities but its chemotactic properties remain unchanged whilst its ability to induced the chemokine IL-8 is enhanced.21904558Pubmed2011Structural and Functional Consequences Induced by Post-Translational Modifications in ?-DefensinsBalducci, EBonucci, APicchianti, MPogni, RTalluri, EInt J Pept 2011:59472312060767Pubmed2002ADP ribosylation of human neutrophil peptide-1 regulates its biological propertiesPaone, GWada, AStevens, LAMatin, AHirayama, TLevine, RLMoss, JProc Natl Acad Sci U S A 99:8231-5inferred by electronic annotationIEAGOIEAReactome Database ID Release 759819566Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9819566ReactomeR-MMU-14620541Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1462054.1Humans have 7 alpha defensin genes plus 5 pseudogenes (see HGNC at http://www.genenames.org/genefamilies/DEFA). Alpha-defensins have six cysteines linked 1-6, 2-4, 3-5. The canonical sequence of alpha-defensins in humans is x1-2CXCRx2-3Cx3Ex3GxCx3Gx5CCx1-4, where x represents any amino acid residue. <br>Human alpha-defensins 1-4 are often called human neutrophil peptides (HNP1-4) as they were initially identified in neutrophil primary (azurophilic) granules. Alpha-defensins 5 and 6 (HD5, HD6) are products of Paneth cells. HNP-1 and -3 peptides are 30 residues long, differing only in the first amino acid. They are encoded by the genes DEFA1 and DEFA3 respectively. These exhibit copy number polymorphism, with some individuals having 4-14 copies per diploid genome, while 10-37% of individuals have no copies of DEFA3 (Aldred et al. 2005, Linzmier & Ganz 2005, Ballana et al. 2007). HNP-4, encoded by DEFA4, is 33 amino acids long of which 22 differ from the other HNPs (Wilde et al. 1989). It is a minor component of neutrophil granules compared to HNP1-3. In contrast to DEFA1 and DEFA3, the genes for HNP-4, HD-5 and HD-6 are only found as two copies per diploid genome (Linzmeier & Ganz 2005). HNP-2 is 29 amino acids in length and is the proteolytic product of cleavage of the N-terminal amino acid from either HNP-1 and/or HNP-3 (Selsted et al. 1985). 17214878Pubmed2007Inter-population variability of DEFA3 gene absence: correlation with haplotype structure and population variabilityBallana, EGonzález, JRBosch, NEstivill, XBMC Genomics 8:1415944200Pubmed2005Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3Aldred, PMHollox, EJArmour, JAHum Mol Genet 14:2045-5216039093Pubmed2005Human defensin gene copy number polymorphisms: comprehensive analysis of independent variation in alpha- and beta-defensin regions at 8p22-p23Linzmeier, RMGanz, TGenomics 86:423-304056036Pubmed1985Primary structures of three human neutrophil defensinsSelsted, MEHarwig, SSGanz, TSchilling, JWLehrer, RIJ Clin Invest 76:1436-9inferred by electronic annotationIEAGOIEABeta defensinsBeta defensinsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Beta-defensins are secretedBeta-defensins are secretedThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeReactome DB_ID: 97594721Beta-defensins [Golgi lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefb1 [Golgi lumen]Defb14 [Golgi lumen]Defb4 [Golgi lumen]Converted from EntitySet in ReactomeReactome DB_ID: 97594161Beta-defensins [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefb14 [extracellular region]Reactome Database ID Release 759759474Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759474ReactomeR-MMU-14713221Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471322.1Beta defensin precursors are more simple in structure than those of alpha defensins, having a signal sequence, a short or absent propiece and the mature defensin sequence at the C-terminus. The signal sequence is cleaved off by a signal peptidase in the endoplasmic reticulum (Ganz 2003). Mature beta defensins 1, 2, 3, and 4 are secreted primarily by epithelial cells but are also produced by some immune cells such as monocytes, macrophages and dendritic cells (Duits et al. 2000, Ryan et al. 2003).9541493Pubmed1998Human beta-defensin-1: an antimicrobial peptide of urogenital tissuesValore, EVPark, CHQuayle, AJWiles, KRMcCray PB, JrGanz, TJ Clin Invest 101:1633-4215019211Pubmed2003Detection of HBD1 peptide in peripheral blood mononuclear cell subpopulations by intracellular flow cytometryRyan, LKDiamond, GAmrute, SFeng, ZWeinberg, AFitzgerald-Bocarsly, PPeptides 24:1785-9421122132Pubmed2010Tissue-specific human beta-defensins (HBD)1, HBD2, and HBD3 secretion from human extra-placental membranes stimulated with Escherichia coliGarcia-Lopez, GFlores-Espinosa, PZaga-Clavellina, VReprod Biol Endocrinol 8:14612153515Pubmed2002Expression of beta-defensin 1 and 2 mRNA by human monocytes, macrophages and dendritic cellsDuits, LARavensbergen, BRademaker, MHiemstra, PSNibbering, PHImmunology 106:517-25inferred by electronic annotationIEAGOIEABeta-defensins bind microbial membranes causing disruptionBeta-defensins bind microbial membranes causing disruptionThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 14620491Converted from EntitySet in ReactomeReactome DB_ID: 97594161Reactome DB_ID: 97594181Beta-defensins:anionic phospholipids [plasma membrane]Beta-defensins:anionic phospholipidsReactome DB_ID: 14620491Converted from EntitySet in ReactomeReactome DB_ID: 97594161Reactome Database ID Release 759759418Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759418ReactomeR-MMU-14713721Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471372.1Reactome Database ID Release 759759420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759420ReactomeR-MMU-14672691Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1467269.1Binding and disruption of microbial membranes is widely believed to be the primary mechanism of action for beta-defensins. There is no direct evidence of this, but a growing number of studies support this model (Pazgier et al. 2006). Beta-defensins have antimicrobial properties that correlate with membrane permeabilization effects (Antcheva et al. 2004, Sahl et al. 2005, Yenugu et al. 2004). The sensitivity of microbes to beta-defensins correlates with the lipid composition of the membrane; more negatively-charged lipids correlate with larger beta-defensin 103-induced changes in membrane capacitance (Bohling et al. 2006). Beta-defensin-103 was observed to give rise to ionic currents in Xenopus membranes (Garcia et al. 2001) and cell wall perforation was observed in S. aureus when treated with HBD-3 (Harder et al. 2001). Two models explain how membrane disruption takes place. The 'pore model' postulates that beta-defenisns form transmembrane pores in a similar manner to alpha-defensins, while the 'carpet model' suggests that beta-defensins act as detergents, causing a less organised disruption. Beta-defensins have a structure that is topologically distinct from that of alpha-defensins, suggesting a different mode of dimerization and an electrostatic charge-based mechanism of membrane permeabilization rather than a mechanism based on formation of bilayer-spanning pores (Hoover et al. 2000).14742239Pubmed2004Effects of positively selected sequence variations in human and Macaca fascicularis beta-defensins 2 on antimicrobial activityAntcheva, NBoniotto, MZelezetsky, IPacor, SVerga Falzacappa, MVCrovella, STossi, AAntimicrob Agents Chemother 48:685-810906336Pubmed2000The structure of human beta-defensin-2 shows evidence of higher order oligomerizationHoover, DMRajashankar, KRBlumenthal, RPuri, AOppenheim, JJChertov, OlegLubkowski, JJ Biol Chem 275:32911-811702237Pubmed2001Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity. Its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattractionGarcía, JRJaumann, FSchulz, SKrause, ARodríguez-Jiménez, JForssmann, UAdermann, KnutKlüver, EVogelmeier, CBecker, DHedrich, RForssmann, WGBals, RCell Tissue Res 306:257-6411085990Pubmed2001Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibioticHarder, JBartels, JChristophers, ESchroder, JMJ Biol Chem 276:5707-1315033915Pubmed2004The androgen-regulated epididymal sperm-binding protein, human beta-defensin 118 (DEFB118) (formerly ESC42), is an antimicrobial beta-defensinYenugu, SHamil, KGRadhakrishnan, YFrench, FSHall, SHEndocrinology 145:3165-7315582982Pubmed2005Mammalian defensins: structures and mechanism of antibiotic activitySahl, HGPag, UBonness, SWagner, SAntcheva, NTossi, AJ Leukoc Biol 77:466-7516634647Pubmed2006Lipid-specific membrane activity of human beta-defensin-3Böhling, AHagge, SORoes, SPodschun, RSahly, HHarder, JSchröder, JMGrötzinger, JSeydel, UGutsmann, TBiochemistry 45:5663-70inferred by electronic annotationIEAGOIEABeta-defensins 1, 4A and 103 bind CCR6Beta-defensins 1, 4A and 103 bind CCR6This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97320581UniProt:O54689Ccr6UniProtO546891EQUAL374EQUALConverted from EntitySet in ReactomeReactome DB_ID: 97594761Beta defensins 1,4A,103 [extracellular region]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityDefb14 [extracellular region]Defb1 [extracellular region]Defb4 [extracellular region]Reactome DB_ID: 97594781Beta-defensins 1,4A,103:CCR6 [plasma membrane]Beta-defensins 1,4A,103:CCR6Reactome DB_ID: 973205811EQUAL374EQUALConverted from EntitySet in ReactomeReactome DB_ID: 97594761Reactome Database ID Release 759759478Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759478ReactomeR-MMU-14713431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471343.1Reactome Database ID Release 759759480Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9759480ReactomeR-MMU-14713381Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1471338.1The chemotactic activity of beta-defensins 1, 4A and 103 (hBD1-3) for immune and inflammatory cells such as memory T cells and immature dendritic cells is mediated through binding to the chemokine receptor CCR6.10521347Pubmed1999Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6Yang, DChertov, OlegBykovskaia, SNChen, QBuffo, MJShogan, JAnderson, MSchröder, JMWang, JMHoward, OMOppenheim, JJScience 286:525-811934878Pubmed2002Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathwayNiyonsaba, FIwabuchi, KMatsuda, HOgawa, HNagaoka, IInt Immunol 14:421-610914484Pubmed2000Human neutrophil defensins selectively chemoattract naive T and immature dendritic cellsYang, DChen, QChertov, OlegOppenheim, JJJ Leukoc Biol 68:9-14inferred by electronic annotationIEAGOIEABeta defensin 103 activates TLR1:TLR2Beta defensin 103 activates TLR1:TLR2This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Reactome DB_ID: 97593881UniProt:Q7TNV9Defb1423EQUAL67EQUALReactome DB_ID: 97646781TLR1:TLR2 [plasma membrane]TLR1:TLR2Reactome DB_ID: 97646761UniProt:Q9EPQ1Tlr1UniProtQ9EPQ125EQUAL786EQUALReactome DB_ID: 97646721UniProt:Q9QUN7Tlr2UniProtQ9QUN719EQUAL784EQUALReactome Database ID Release 759764678Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764678ReactomeR-MMU-1689461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-168946.1Reactome DB_ID: 97646801Beta defensin 103:TLR1:TLR2 [plasma membrane]Beta defensin 103:TLR1:TLR2Reactome DB_ID: 9759388123EQUAL67EQUALReactome DB_ID: 97646781Reactome Database ID Release 759764680Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764680ReactomeR-MMU-19746731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1974673.1Reactome Database ID Release 759764682Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9764682ReactomeR-MMU-19746761Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1974676.1Beta defensin 103 (hBD-3) can induce expression of the costimulatory molecules CD80, CD86 and CD40 on monocytes and myeloid dendritic cells in a Toll-like receptor (TLR)-dependent manner. Activation by hBD-3 is mediated by an interaction that requires TLRs 1 and 2 (Funderburg et al. 2007, 2011).21896010Pubmed2011The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human ?-defensin-3 differentially induce interleukin-10 and nuclear factor-?B signalling patterns in human monocytesFunderburg, NTJadlowsky, JKLederman, MMFeng, ZWeinberg, ASieg, SFImmunology 134:151-6018006661Pubmed2007Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2Funderburg, NLederman, MMFeng, ZDrage, MGJadlowsky, JHarding, CVWeinberg, ASieg, SFProc Natl Acad Sci U S A 104:18631-5inferred by electronic annotationIEAGOIEAReactome Database ID Release 759819570Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9819570ReactomeR-MMU-14619571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461957.1Humans have 38 beta-defensin genes plus 9-10 pseudogenes (details available on the HGNC website at http://www.genenames.org/genefamilies/DEFB). Many beta-defensins are encoded by recently duplicated genes giving rise to identical transcripts. Nomenclature is confusing and currently in transition. Uniprot recommended names are used throughout this pathway.<br>Many beta-defensins show expression that correlates with infection (Sahl et al. 2005, Pazgier et al. 2006). All so far characterized beta-defensins, i.e. beta-defensin 1 (hBD1), 4A (hBD2), 103 (hBD3), 104 (hBD4), 106 (hBD6), 118 (hBD18) and 128 (hBD28) have antimicrobial properties (Pazgier et al. 2006). For beta-defensins 4A, 103 and 118 (hBD2, 3, and 18) this has been shown to correlate with membrane permeabilization effects (Antcheva et al. 2004, Sahl et al. 2005, Yenugu et al. 2004). Electrostatic interaction and disruption of microbial membranes is widely believed to the primary mechanism of action for beta-defensins. Two models explain how membrane disruption takes place, the 'pore model' which postulates that beta-defensins form transmembrane pores in a similar manner to alpha-defensins, and the 'carpet model', which suggests that beta-defensins act as detergents. Beta-defensins contain 6 conserved cysteine residues that in beta-defensins 1, 4A and 103 (hBD1-3) are experimentally confirmed to be cross-linked 1-5, 2-4, 3-6. The canonical sequence for beta-defensins is x2-10Cx5-6(G/A)xCX3-4Cx9-13Cx4-7CCxn. Structurally they are similar to alpha-defensins but with much shorter pre-regions. Though dimerization of some beta-defensins has been reported this is not the case for all and it is unclear whether it is required for function. The majority of functional studies have focused on beta-defensin 103 (hBD3), which has the most significant antimicrobial activity at physiological salt concentrations (Harder et al. 2001). Beta-defensin 103 is highly cationic with a net charge of +11 e0. It exhibits broad-spectrum antimicrobial activity against gram-positive bacteria and some gram-negative bacteria (Harder et al. 2001), though some species are highly resistant (Sahly et al. 2003). Sensitivity correlates with lipid composition of the membrane, with more negatively-charged lipids correlating with larger beta-defensin 103-induced changes in membrane capacitance (Bohling et al. 2006). Though membrane disruption is widely believed to be the primary mechanism of action of beta-defensins they have other antimicrobial properties, such as inhibition of cell wall biosynthesis (Sass et al. 2010), and chemoattractant effects (Yang et al. 1999, Niyonsaba et al. 2002, 2004). The chemotactic activity of beta-defensins 1, 4A and 103 (hBD1-3) for memory T cells and immature DCs is mediated through binding to the chemokine receptor CCR6 and probably another unidentified Gi-coupled receptor (Yang et al. 1999, 2000). <br> <br>Like defensins, the human cathelicidin LL37 peptide is rich in positively-charged residues (Lehrer & Ganz 2002).<br>Expression of certain beta-defensins can be induced in response to various signals, such as bacteria, pathogen-associated molecular patterns (PAMPs), or proinflammatory cytokines (Ganz 2003, Yang et al. 2004). Like the alpha-defensins, copy number variation has been reported for DEFB4, DEFB103 and DEFB104 with individuals having 2-12 copies per diploid genome. In contrast DEFB1 does not show such variation but exhibits a number of SNPs (Hollox et al. 2003, Linzmier & Ganz 2005).15009427Pubmed2004Human beta-defensin-2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophilsNiyonsaba, FOgawa, HNagaoka, IImmunology 111:273-8112916016Pubmed2003Extensive normal copy number variation of a beta-defensin antimicrobial-gene clusterHollox, EJArmour, JABarber, JCAm J Hum Genet 73:591-60020385753Pubmed2010Human beta-defensin 3 inhibits cell wall biosynthesis in StaphylococciSass, VSchneider, TWilmes, MKörner, CTossi, ANovikova, NShamova, OSahl, HGInfect Immun 78:2793-80012709350Pubmed2003Burkholderia is highly resistant to human Beta-defensin 3Sahly, HSchubert, SHarder, JRautenberg, PUllmann, USchröder, JPodschun, RAntimicrob Agents Chemother 47:1739-4111753073Pubmed2002Cathelicidins: a family of endogenous antimicrobial peptidesLehrer, RIGanz, TCurr Opin Hematol 9:18-22inferred by electronic annotationIEAGOIEAReactome Database ID Release 759819568Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9819568ReactomeR-MMU-14619731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1461973.1The defensins are a family of antimicrobial cationic peptide molecules which in mammals have a characteristic beta-sheet-rich fold and framework of six disulphide-linked cysteines (Selsted & Ouellette 2005, Ganz 2003). Human defensin peptides have two subfamilies, alpha- and beta-defensins, differing in the length of peptide chain between the six cysteines and the order of disulphide bond pairing between them. A third subfamily, the theta defensins, is derived from alpha-defensins prematurely truncated by a stop codon between the third and fourth cysteine residues. The translated products are shortened to nonapeptides, covalently dimerized by disulfide linkages, and cyclized via new peptide bonds between the first and ninth residues. Humans have one pseudogene but no translated representatives of the theta class.<br>In solution most alpha and beta defensins are monomers but can form dimers and higher order structures. <br><br>The primary cellular sources of defensins are neutrophils, epithelial cells and intestinal Paneth cells.Those expressed in neutrophils and the gut are predominantly constitutive, while those in epithelial tissues such as skin are often inducible by proinflammatory stimuli such as LPS or TNF-alpha.<br><br>Defensins are translated as precursor polypeptides that include a typical signal peptide or prepiece that is cleaved in the Golgi body, and a propiece, cleaved by differing mechanisms to produce the mature defensin. Mature defensin peptides can be further processed by removal of individual N-terminal residues (Yang et al. 2004). This may be a mechanism to broaden the activity profile of defensins (Ghosh et al. 2002).<br><br>Defensins have direct antimicrobial effects and kill a wide range of Gram-positive and negative bacteria, fungi and some viruses. The primary antimicrobial action of defensins is permeabilization of microbial target membranes but several additional mechanisms have been suggested (Brogden 2005, Wilmes et al. 2011). Defensins and related antimicrobial peptides such as cathelicidin bridge the innate and acquired immune responses. In addition to their antimicrobial properties, cathelicidin and several defensins show receptor-mediated chemotactic activity for immune cells such as monocytes, T cells or immature DCs, induce cytokine production by monocytes and epithelial cells, modulate angiogenesis and stimulate wound healing (Yang et al. 1999, 2000, 2004, Rehaume & Hancock 2008, Yeung et al. 2011).15908936Pubmed2005Mammalian defensins in the antimicrobial immune responseSelsted, MEOuellette, AJNat Immunol 6:551-721573784Pubmed2011Multifunctional cationic host defence peptides and their clinical applicationsYeung, ATGellatly, SLHancock, RECell Mol Life Sci 68:2161-7621617811Pubmed2011Antibiotic activities of host defense peptides: more to it than lipid bilayer perturbationWilmes, MCammue, BPSahl, HGThevissen, KNat Prod Rep 28:1350-815703760Pubmed2005Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?Brogden, KANat Rev Microbiol 3:238-5015372083Pubmed2004Primate defensinsLehrer, RINat Rev Microbiol 2:727-38inferred by electronic annotationIEAGOIEA