Antimicrobial peptides (Homo sapiens)

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29, 5913, 6257, 6326, 66305, 7, 2540-4238, 61, 7165, 8520, 28, 5038, 61, 7123, 4449, 71, 73, 839, 15, 22, 31, 36...11785216, 18, 7437, 7940, 428, 8635, 456, 67, 8143, 552, 19, 753, 73, 8312, 144, 47, 548410, 52, 82808, 32, 51, 649, 15, 22, 31, 36...65, 851, 39, 648421, 46, 601, 3934, 7726, 66cell wallphagocytic vesicle lumencell wallhost cell cytosolDCD(63-110) CHGA-derivedpeptide:bacterialanionic lipidsHTN1,3,5:bacterialphospholipidsEPC:bacterialsurfaceAnionicphospholipids:microbial cell surfaceMicrobial cell surface PLA2G2A:Ca2+Zn2+ LCN2 DefensinsAnionic phospholipids RNASE6 GlcNac-(1-->4)MurNAc-L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 hC-EPPIN CAMP(134-170)GlcNAc(1-->4)MurNAc:L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 S100A7, S100A7A:Ca2+DCD(63-110)2.5DHBA Microbial cell surface DCD peptidesheptose REG3A(38-175) H+Anionic phospholipids REG3A(38-175) HTN3(20-43) PGLYRP1 PI3RNASE8 REG3A(38-175) Microbial cell surface BPIFB6 HTN3 HTN1 Microbial cell surface HTN1(31-57) Na+ CAMP(31-170)REG3A(38-175):anionic phospholipidsLTFPGLYRP2 dimerRNASE6 H+GlcNAc(1-->4)MurNAc:L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 BPIFB6 Fe3+RNASE8 CLU(23-227) HTN1(31-57) PGLYRP4 Ca2+ H2OBPIFA2 REG3Ahexamer:anionicphospholipidHTN3 Microbial cellsurfaceCAMP(134-170) REG3A(38-175) BPIFA1 hC239-SEMG1 BPIFB1 LYZLEAP2 ATOX1:Cu1+ELANE, CTSG, PRTN3BPIFA1 (GlcNAc+MurNac)nGNLY Zn2+LEAP2:bacterialphospholipidsPiLCN2:2,5DHBAREG3A(27-37) hC239-SEMG1 BPIFB4 hC-EPPIN PRTN3Anionic phospholipids RNASE3 PGLYRP3,4 dimersAnionic phospholipids Microbial cell surface CHGA(19-94) Microbial cell surface CAMP(134-170):microbial cell surfaceTrypsin 2, 3HTN3(20-43) S100A9 Ca2+ LPSBPIPGLYRP3,4dimer:peptidoglycanPGLYRP2 PLA2G2A:phospholipidsZn2+ PI3(61-117) Microbial cell surface LEAP2RNASE6 PI3(61-117) CLU(228-449) S100A8 Microbial cell surface LCN2:2,5DHBA:Fe3+RNASEs3,6,7,(8):LPS,PGNGlcNAc(1-->4)MurNAc:L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 BPIFA/BPIFBDCD(63-110) REG3G(27-37) ELANE,CTSG,PRTN3:microbialcell surfacePDZD11 PRSS3 Ca2+ PGLYRP2 H2OCa2+ CHGA(19-94) Ca2+ MurNAc:PeptidePGLYRP3 RNASE3,RNASE7,RNASE6,(RNASE8)Divalent metalstransported byNRAMP1Zn2+ Anionic phospholipids DCD(63-110) Mn2+ REG3A(27-37)/REG3G(27-37)heptose beta-D-galactofuranosyl 2.5DHBA PGLYRP1 dimerS100A7,S100A7A:Ca2+:Zn2+LCN2 CTSG HTN1 Anionic phospholipids RNASE7 REG3A(27-175)/REG3G(27-175)Microbial cell surface GNLY:bacterialanionic lipidsDCD(20-62)Microbial cell surface GlcNAc(1-->4)MurNAc:L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 DCD(20-110)LTF S100A9 CLU(23-227) Microbial cell surface Mn2+ DCD:anionicphospholipidunknown peptidaseHTN3 LPS CO3(2-) PGLYRP4 Microbial cell surface Anionic phospholipids Fe3+ Anionicphospholipids:microbial cell surfaceLTF HTN3 GNLY:bacterialanionic lipidsCa2+ HTN1 PI3(23-117) REG3A(27-175) HTN3(20-43) peptidoglycan-NHAc Ca2+ SSA2 Anionic phospholipids GNLYDCDhexamer:Zn(2+):anionic phospholipidsDivalent metalstransported byNRAMP1ITLN1 S100A7 KDO ELANE ADPLTF:2xFe3+:2xCO3(2-)REG3G(38-175) INTL1:bacterialglycanFe3+ ATPZn2+BPI RNASE3 Cu1+Microbial cell surface S100A8 EPPIN:SEMG1:LTF:CLUH2OPLA2G2A REG3G(38-175) PGLYRP3 L-Ala-gamma-D-Glu-L-Lys-D-Alapeptidoglycan-NHAc Zn2+ REG3G(27-175) INTL1 ligandsRNASEs3,6,7,(8):anionicphospholipidsAnionic phospholipids GlcNac-(1-->4)MurNAc-L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2SSA1 BPI:LPSCLU(228-449) Microbial cell surface PRTN3 PGLYRP1dimer:peptidoglycanFe2+ LYZ HTN5,(HTN1, HTN3)ATP7A:PDZD11S100A8:S100A9:Ca2+:Zn2+Mn2+HTN1,3,5S100A7A ATP7A GNLYDCD(63-110):anionicphospholipidCHGA fragmentsCTSG betaGlcNAcAnionic phospholipids Fe3+HTN1 PRSS2(24-247) S100A8:S100A9:Ca2+:Mn2+:Na+CO3(2-)BPIFA2 REG3A(38-175)PGLYRP2:peptidoglycanRNASE8 ITLN1 trimer:Ca2+ITLN1 Zn2+ BPIFB2 CHGA(370-390) DCD(63-109) Microbial cell surface S100A7A HTN3(20-43) RNASE3 Microbial cell surface PI3(23-117) ATOX1Anionic phospholipids Microbial cell surface DCD(63-110) DCD(63-109) HTN5, (HTN1,HTN3):SSA1,SSA2RNASE7 LYZ:PGNREG3A(38-175),REG3G(38-175):peptidoglycanCu1+ Anionic phospholipids LPS ELANE S100A8 SLC11A1LPSCHGA(370-390) PLA2G2A BPIFB4 MurNAc Anionic phospholipids RNASE7 Ca2+ BPIFB1 DCD(63-109)Zn2+PRTN3 REG3A(38-175),REG3G(38-175)LPS, PGNLPS SSA1,SSA2PI3:LPSLTF Na+SSA1 beta-D-galactofuranosyl GlcNac-(1-->4)MurNAc-L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2S100A9 SSA2 Microbial cell surface ATOX1 Ca2+ S100A7 LPS Fe2+ Anionic phospholipids GNLY KDO PGLYRP1 Peptide Mn2+ BPIFA/BPIFB:bacterial cellBPIFB2 S100A8:S100A9:Ca2+32, 51312427845573, 8312122451125, 733703149, 835310, 17, 56, 7658685, 7, 2584586410, 52, 5649, 69, 8317, 52, 56, 76


Antimicrobial peptides (AMPs) are small molecular weight proteins with broad spectrum of antimicrobial activity against bacteria, viruses, and fungi (Zasloff M 2002; Radek K & Gallo R 2007). The majority of known AMPs are cationic peptides with common structural characteristics where domains of hydrophobic and cationic amino acids are spatially arranged into an amphipathic design, which facilitates their interaction with bacterial membranes (Shai Y 2002; Yeaman MR & Yount NY 2003; Brown KL & Hancock RE 2006; Dennison SR et al. 2005; Zelezetsky I & Tossi A 2006). It is generally excepted that the electrostatic interaction facilitates the initial binding of the positively charged peptides to the negatively charged bacterial membrane. Moreover, the structural amphiphilicity of AMPs is thought to promote their integration into lipid bilayers of pathogenic cells, leading to membrane disintegration and finally to the microbial cell death. In addition to cationic AMPs a few anionic antimicrobial peptides have been found in humans, however their mechanism of action remains to be clarified (Lai Y et al. 2007; Harris F et al. 2009; Paulmann M et al. 2012). Besides the direct neutralizing effects on bacteria AMPs may modulate cells of the adaptive immunity (neutrophils, T-cells, macrophages) to control inflammation and/or to increase bacterial clearance.

AMPs have also been referred to as cationic host defense peptides, anionic antimicrobial peptides/proteins, cationic amphipathic peptides, cationic AMPs, host defense peptides and alpha-helical antimicrobial peptides (Brown KL & Hancock RE 2006; Harris F et al. 2009; Groenink J et al. 1999; Bradshaw J 2003; Riedl S et al. 2011; Huang Y et al. 2010).<p>The Reactome module describes the interaction events of various types of human AMPs, such as cathelicidin, histatins and neutrophil serine proteases, with conserved patterns of microbial membranes at the host-pathogen interface. The module includes also proteolytic processing events for dermcidin (DCD) and cathelicidin (CAMP) that become functional upon cleavage. In addition, the module highlights an AMP-associated ability of the host to control metal quota at inflammation sites to influence host-pathogen interactions. View original pathway at:Reactome.</div>


Pathway is converted from Reactome ID: 6803157
Reactome version: 66
Reactome Author 
Reactome Author: Shamovsky, Veronica

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  1. Zhang Y, van der Fits L, Voerman JS, Melief MJ, Laman JD, Wang M, Wang H, Wang M, Li X, Walls CD, Gupta D, Dziarski R.; ''Identification of serum N-acetylmuramoyl-l-alanine amidase as liver peptidoglycan recognition protein 2.''; PubMed Europe PMC Scholia
  2. Moreau T, Baranger K, Dadé S, Dallet-Choisy S, Guyot N, Zani ML.; ''Multifaceted roles of human elafin and secretory leukocyte proteinase inhibitor (SLPI), two serine protease inhibitors of the chelonianin family.''; PubMed Europe PMC Scholia
  3. Burian M, Schittek B.; ''The secrets of dermcidin action.''; PubMed Europe PMC Scholia
  4. Djoko KY, Ong CL, Walker MJ, McEwan AG.; ''The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens.''; PubMed Europe PMC Scholia
  5. León R, Murray JI, Cragg G, Farnell B, West NR, Pace TC, Watson PH, Bohne C, Boulanger MJ, Hof F.; ''Identification and characterization of binding sites on S100A7, a participant in cancer and inflammation pathways.''; PubMed Europe PMC Scholia
  6. Elsbach P, Weiss J.; ''Role of the bactericidal/permeability-increasing protein in host defence.''; PubMed Europe PMC Scholia
  7. Brodersen DE, Nyborg J, Kjeldgaard M.; ''Zinc-binding site of an S100 protein revealed. Two crystal structures of Ca2+-bound human psoriasin (S100A7) in the Zn2+-loaded and Zn2+-free states.''; PubMed Europe PMC Scholia
  8. Royet J, Dziarski R.; ''Peptidoglycan recognition proteins: pleiotropic sensors and effectors of antimicrobial defences.''; PubMed Europe PMC Scholia
  9. Rudolph B, Podschun R, Sahly H, Schubert S, Schröder JM, Harder J.; ''Identification of RNase 8 as a novel human antimicrobial protein.''; PubMed Europe PMC Scholia
  10. Damo SM, Kehl-Fie TE, Sugitani N, Holt ME, Rathi S, Murphy WJ, Zhang Y, Betz C, Hench L, Fritz G, Skaar EP, Chazin WJ.; ''Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.''; PubMed Europe PMC Scholia
  11. Sørensen OE, Follin P, Johnsen AH, Calafat J, Tjabringa GS, Hiemstra PS, Borregaard N.; ''Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3.''; PubMed Europe PMC Scholia
  12. Wesener DA, Wangkanont K, McBride R, Song X, Kraft MB, Hodges HL, Zarling LC, Splain RA, Smith DF, Cummings RD, Paulson JC, Forest KT, Kiessling LL.; ''Recognition of microbial glycans by human intelectin-1.''; PubMed Europe PMC Scholia
  13. Radek KA, Lopez-Garcia B, Hupe M, Niesman IR, Elias PM, Taupenot L, Mahata SK, O'Connor DT, Gallo RL.; ''The neuroendocrine peptide catestatin is a cutaneous antimicrobial and induced in the skin after injury.''; PubMed Europe PMC Scholia
  14. Tsuji S, Uehori J, Matsumoto M, Suzuki Y, Matsuhisa A, Toyoshima K, Seya T.; ''Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall.''; PubMed Europe PMC Scholia
  15. Boix E, Torrent M, Sánchez D, Nogués MV.; ''The antipathogen activities of eosinophil cationic protein.''; PubMed Europe PMC Scholia
  16. Stapels DA, Geisbrecht BV, Rooijakkers SH.; ''Neutrophil serine proteases in antibacterial defense.''; PubMed Europe PMC Scholia
  17. Leukert N, Vogl T, Strupat K, Reichelt R, Sorg C, Roth J.; ''Calcium-dependent tetramer formation of S100A8 and S100A9 is essential for biological activity.''; PubMed Europe PMC Scholia
  18. Pham CT.; ''Neutrophil serine proteases: specific regulators of inflammation.''; PubMed Europe PMC Scholia
  19. Williams SE, Brown TI, Roghanian A, Sallenave JM.; ''SLPI and elafin: one glove, many fingers.''; PubMed Europe PMC Scholia
  20. Bingle CD, Craven CJ.; ''PLUNC: a novel family of candidate host defence proteins expressed in the upper airways and nasopharynx.''; PubMed Europe PMC Scholia
  21. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK.; ''The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition.''; PubMed Europe PMC Scholia
  22. Spencer JD, Schwaderer AL, Wang H, Bartz J, Kline J, Eichler T, DeSouza KR, Sims-Lucas S, Baker P, Hains DS.; ''Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract.''; PubMed Europe PMC Scholia
  23. Kishi F, Nobumoto M.; ''Identification of natural resistance-associated macrophage protein in peripheral blood lymphocytes.''; PubMed Europe PMC Scholia
  24. Campbell EJ, Silverman EK, Campbell MA.; ''Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity.''; PubMed Europe PMC Scholia
  25. Murray JI, Tonkin ML, Whiting AL, Peng F, Farnell B, Cullen JT, Hof F, Boulanger MJ.; ''Structural characterization of S100A15 reveals a novel zinc coordination site among S100 proteins and altered surface chemistry with functional implications for receptor binding.''; PubMed Europe PMC Scholia
  26. Surna A, Kubilius R, Sakalauskiene J, Vitkauskiene A, Jonaitis J, Saferis V, Gleiznys A.; ''Lysozyme and microbiota in relation to gingivitis and periodontitis.''; PubMed Europe PMC Scholia
  27. Gazzano-Santoro H, Parent JB, Grinna L, Horwitz A, Parsons T, Theofan G, Elsbach P, Weiss J, Conlon PJ.; ''High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide.''; PubMed Europe PMC Scholia
  28. Bingle CD, LeClair EE, Havard S, Bingle L, Gillingham P, Craven CJ.; ''Phylogenetic and evolutionary analysis of the PLUNC gene family.''; PubMed Europe PMC Scholia
  29. Bahar AA, Ren D.; ''Antimicrobial peptides.''; PubMed Europe PMC Scholia
  30. Birts CN, Barton CH, Wilton DC.; ''Catalytic and non-catalytic functions of human IIA phospholipase A2.''; PubMed Europe PMC Scholia
  31. Torrent M, Badia M, Moussaoui M, Sanchez D, Nogués MV, Boix E.; ''Comparison of human RNase 3 and RNase 7 bactericidal action at the Gram-negative and Gram-positive bacterial cell wall.''; PubMed Europe PMC Scholia
  32. Cho S, Wang Q, Swaminathan CP, Hesek D, Lee M, Boons GJ, Mobashery S, Mariuzza RA.; ''Structural insights into the bactericidal mechanism of human peptidoglycan recognition proteins.''; PubMed Europe PMC Scholia
  33. Lehrer RI.; ''Primate defensins.''; PubMed Europe PMC Scholia
  34. Cash HL, Whitham CV, Behrendt CL, Hooper LV.; ''Symbiotic bacteria direct expression of an intestinal bactericidal lectin.''; PubMed Europe PMC Scholia
  35. Rivas-Santiago B, Hernandez-Pando R, Carranza C, Juarez E, Contreras JL, Aguilar-Leon D, Torres M, Sada E.; ''Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells.''; PubMed Europe PMC Scholia
  36. Becknell B, Eichler TE, Beceiro S, Li B, Easterling RS, Carpenter AR, James CL, McHugh KM, Hains DS, Partida-Sanchez S, Spencer JD.; ''Ribonucleases 6 and 7 have antimicrobial function in the human and murine urinary tract.''; PubMed Europe PMC Scholia
  37. Krause A, Sillard R, Kleemeier B, Klüver E, Maronde E, Conejo-García JR, Forssmann WG, Schulz-Knappe P, Nehls MC, Wattler F, Wattler S, Adermann K.; ''Isolation and biochemical characterization of LEAP-2, a novel blood peptide expressed in the liver.''; PubMed Europe PMC Scholia
  38. Baechle D, Flad T, Cansier A, Steffen H, Schittek B, Tolson J, Herrmann T, Dihazi H, Beck A, Mueller GA, Mueller M, Stevanovic S, Garbe C, Mueller CA, Kalbacher H.; ''Cathepsin D is present in human eccrine sweat and involved in the postsecretory processing of the antimicrobial peptide DCD-1L.''; PubMed Europe PMC Scholia
  39. Wang ZM, Li X, Cocklin RR, Wang M, Wang M, Fukase K, Inamura S, Kusumoto S, Gupta D, Dziarski R.; ''Human peptidoglycan recognition protein-L is an N-acetylmuramoyl-L-alanine amidase.''; PubMed Europe PMC Scholia
  40. Melino S, Santone C, Di Nardo P, Sarkar B.; ''Histatins: salivary peptides with copper(II)- and zinc(II)-binding motifs: perspectives for biomedical applications.''; PubMed Europe PMC Scholia
  41. De Smet K, Contreras R.; ''Human antimicrobial peptides: defensins, cathelicidins and histatins.''; PubMed Europe PMC Scholia
  42. Oppenheim FG, Xu T, McMillian FM, Levitz SM, Diamond RD, Offner GD, Troxler RF.; ''Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans.''; PubMed Europe PMC Scholia
  43. Yenugu S, Richardson RT, Sivashanmugam P, Wang Z, O'rand MG, French FS, Hall SH.; ''Antimicrobial activity of human EPPIN, an androgen-regulated, sperm-bound protein with a whey acidic protein motif.''; PubMed Europe PMC Scholia
  44. Kishi F.; ''Isolation and characterization of human Nramp cDNA.''; PubMed Europe PMC Scholia
  45. van der Does AM, Bergman P, Agerberth B, Lindbom L.; ''Induction of the human cathelicidin LL-37 as a novel treatment against bacterial infections.''; PubMed Europe PMC Scholia
  46. Flo TH, Smith KD, Sato S, Rodriguez DJ, Holmes MA, Strong RK, Akira S, Aderem A.; ''Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron.''; PubMed Europe PMC Scholia
  47. Hodgkinson V, Petris MJ.; ''Copper homeostasis at the host-pathogen interface.''; PubMed Europe PMC Scholia
  48. Simanski M, Köten B, Schröder JM, Gläser R, Harder J.; ''Antimicrobial RNases in cutaneous defense.''; PubMed Europe PMC Scholia
  49. Jung HH, Yang ST, Sim JY, Lee S, Lee JY, Kim HH, Shin SY, Kim JI.; ''Analysis of the solution structure of the human antibiotic peptide dermcidin and its interaction with phospholipid vesicles.''; PubMed Europe PMC Scholia
  50. Bingle CD, Bingle L, Craven CJ.; ''Distant cousins: genomic and sequence diversity within the BPI fold-containing (BPIF)/PLUNC protein family.''; PubMed Europe PMC Scholia
  51. Guan R, Roychowdury A, Ember B, Kumar S, Boons GJ, Mariuzza RA.; ''Crystal structure of a peptidoglycan recognition protein (PGRP) in complex with a muramyl tripeptide from Gram-positive bacteria.''; PubMed Europe PMC Scholia
  52. Gagnon DM, Brophy MB, Bowman SE, Stich TA, Drennan CL, Britt RD, Nolan EM.; ''Manganese binding properties of human calprotectin under conditions of high and low calcium: X-ray crystallographic and advanced electron paramagnetic resonance spectroscopic analysis.''; PubMed Europe PMC Scholia
  53. Wernimont AK, Huffman DL, Lamb AL, O'Halloran TV, Rosenzweig AC.; ''Structural basis for copper transfer by the metallochaperone for the Menkes/Wilson disease proteins.''; PubMed Europe PMC Scholia
  54. Festa RA, Thiele DJ.; ''Copper at the front line of the host-pathogen battle.''; PubMed Europe PMC Scholia
  55. Wang Z, Widgren EE, Richardson RT, O'Rand MG.; ''Characterization of an eppin protein complex from human semen and spermatozoa.''; PubMed Europe PMC Scholia
  56. Korndörfer IP, Brueckner F, Skerra A.; ''The crystal structure of the human (S100A8/S100A9)2 heterotetramer, calprotectin, illustrates how conformational changes of interacting alpha-helices can determine specific association of two EF-hand proteins.''; PubMed Europe PMC Scholia
  57. Mukherjee S, Partch CL, Lehotzky RE, Whitham CV, Chu H, Bevins CL, Gardner KH, Hooper LV.; ''Regulation of C-type lectin antimicrobial activity by a flexible N-terminal prosegment.''; PubMed Europe PMC Scholia
  58. Pepys MB, Hawkins PN, Booth DR, Vigushin DM, Tennent GA, Soutar AK, Totty N, Nguyen O, Blake CC, Terry CJ.; ''Human lysozyme gene mutations cause hereditary systemic amyloidosis.''; PubMed Europe PMC Scholia
  59. Yeaman MR, Yount NY.; ''Mechanisms of antimicrobial peptide action and resistance.''; PubMed Europe PMC Scholia
  60. Devireddy LR, Hart DO, Goetz DH, Green MR.; ''A mammalian siderophore synthesized by an enzyme with a bacterial homolog involved in enterobactin production.''; PubMed Europe PMC Scholia
  61. Rieg S, Seeber S, Steffen H, Humeny A, Kalbacher H, Stevanovic S, Kimura A, Garbe C, Schittek B.; ''Generation of multiple stable dermcidin-derived antimicrobial peptides in sweat of different body sites.''; PubMed Europe PMC Scholia
  62. Sugawara M, Resende JM, Moraes CM, Marquette A, Chich JF, Metz-Boutigue MH, Bechinger B.; ''Membrane structure and interactions of human catestatin by multidimensional solution and solid-state NMR spectroscopy.''; PubMed Europe PMC Scholia
  63. Medveczky P, Szmola R, Sahin-Tóth M.; ''Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation.''; PubMed Europe PMC Scholia
  64. Lu X, Wang M, Qi J, Wang H, Li X, Gupta D, Dziarski R.; ''Peptidoglycan recognition proteins are a new class of human bactericidal proteins.''; PubMed Europe PMC Scholia
  65. Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melián A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL.; ''An antimicrobial activity of cytolytic T cells mediated by granulysin.''; PubMed Europe PMC Scholia
  66. Schindler M, Assaf Y, Sharon N, Chipman DM.; ''Mechanism of lysozyme catalysis: role of ground-state strain in subsite D in hen egg-white and human lysozymes.''; PubMed Europe PMC Scholia
  67. Weiss J, Elsbach P, Shu C, Castillo J, Grinna L, Horwitz A, Theofan G.; ''Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria.''; PubMed Europe PMC Scholia
  68. McMichael JW, Roghanian A, Jiang L, Ramage R, Sallenave JM.; ''The antimicrobial antiproteinase elafin binds to lipopolysaccharide and modulates macrophage responses.''; PubMed Europe PMC Scholia
  69. Schittek B, Hipfel R, Sauer B, Bauer J, Kalbacher H, Stevanovic S, Schirle M, Schroeder K, Blin N, Meier F, Rassner G, Garbe C.; ''Dermcidin: a novel human antibiotic peptide secreted by sweat glands.''; PubMed Europe PMC Scholia
  70. Anderson DH, Sawaya MR, Cascio D, Ernst W, Modlin R, Krensky A, Eisenberg D.; ''Granulysin crystal structure and a structure-derived lytic mechanism.''; PubMed Europe PMC Scholia
  71. Schittek B.; ''The multiple facets of dermcidin in cell survival and host defense.''; PubMed Europe PMC Scholia
  72. Pulido D, Arranz-Trullén J, Prats-Ejarque G, Velázquez D, Torrent M, Moussaoui M, Boix E.; ''Insights into the Antimicrobial Mechanism of Action of Human RNase6: Structural Determinants for Bacterial Cell Agglutination and Membrane Permeation.''; PubMed Europe PMC Scholia
  73. Paulmann M, Arnold T, Linke D, Özdirekcan S, Kopp A, Gutsmann T, Kalbacher H, Wanke I, Schuenemann VJ, Habeck M, Bürck J, Ulrich AS, Schittek B.; ''Structure-activity analysis of the dermcidin-derived peptide DCD-1L, an anionic antimicrobial peptide present in human sweat.''; PubMed Europe PMC Scholia
  74. Korkmaz B, Moreau T, Gauthier F.; ''Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions.''; PubMed Europe PMC Scholia
  75. Sallenave JM.; ''Secretory leukocyte protease inhibitor and elafin/trappin-2: versatile mucosal antimicrobials and regulators of immunity.''; PubMed Europe PMC Scholia
  76. Strupat K, Rogniaux H, Van Dorsselaer A, Roth J, Vogl T.; ''Calcium-induced noncovalently linked tetramers of MRP8 and MRP14 are confirmed by electrospray ionization-mass analysis.''; PubMed Europe PMC Scholia
  77. Lehotzky RE, Partch CL, Mukherjee S, Cash HL, Goldman WE, Gardner KH, Hooper LV.; ''Molecular basis for peptidoglycan recognition by a bactericidal lectin.''; PubMed Europe PMC Scholia
  78. Haridas M, Anderson BF, Baker EN.; ''Structure of human diferric lactoferrin refined at 2.2 A resolution.''; PubMed Europe PMC Scholia
  79. Henriques ST, Tan CC, Craik DJ, Clark RJ.; ''Structural and functional analysis of human liver-expressed antimicrobial peptide 2.''; PubMed Europe PMC Scholia
  80. Walch M, Eppler E, Dumrese C, Barman H, Groscurth P, Ziegler U.; ''Uptake of granulysin via lipid rafts leads to lysis of intracellular Listeria innocua.''; PubMed Europe PMC Scholia
  81. Elsbach P.; ''The bactericidal/permeability-increasing protein (BPI) in antibacterial host defense.''; PubMed Europe PMC Scholia
  82. Hayden JA, Brophy MB, Cunden LS, Nolan EM.; ''High-affinity manganese coordination by human calprotectin is calcium-dependent and requires the histidine-rich site formed at the dimer interface.''; PubMed Europe PMC Scholia
  83. Song C, Weichbrodt C, Salnikov ES, Dynowski M, Forsberg BO, Bechinger B, Steinem C, de Groot BL, Zachariae U, Zeth K.; ''Crystal structure and functional mechanism of a human antimicrobial membrane channel.''; PubMed Europe PMC Scholia
  84. Mukherjee S, Zheng H, Derebe MG, Callenberg KM, Partch CL, Rollins D, Propheter DC, Rizo J, Grabe M, Jiang QX, Hooper LV.; ''Antibacterial membrane attack by a pore-forming intestinal C-type lectin.''; PubMed Europe PMC Scholia
  85. Ernst WA, Thoma-Uszynski S, Teitelbaum R, Ko C, Hanson DA, Clayberger C, Krensky AM, Leippe M, Bloom BR, Ganz T, Modlin RL.; ''Granulysin, a T cell product, kills bacteria by altering membrane permeability.''; PubMed Europe PMC Scholia
  86. Cho JH, Fraser IP, Fukase K, Kusumoto S, Fujimoto Y, Stahl GL, Ezekowitz RA.; ''Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity.''; PubMed Europe PMC Scholia


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101534view11:40, 1 November 2018ReactomeTeamreactome version 66
101069view21:22, 31 October 2018ReactomeTeamreactome version 65
100599view19:56, 31 October 2018ReactomeTeamreactome version 64
100149view16:41, 31 October 2018ReactomeTeamreactome version 63
99699view15:10, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99284view12:46, 31 October 2018ReactomeTeamreactome version 62
93538view11:26, 9 August 2017ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
(GlcNAc+MurNac)nR-ALL-6799970 (Reactome)
2.5DHBA MetaboliteCHEBI:17189 (ChEBI)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATOX1 ProteinO00244 (Uniprot-TrEMBL)
ATOX1:Cu1+ComplexR-HSA-3697875 (Reactome)
ATOX1ProteinO00244 (Uniprot-TrEMBL)
ATP7A ProteinQ04656 (Uniprot-TrEMBL)
ATP7A:PDZD11ComplexR-HSA-6803541 (Reactome)
ATPMetaboliteCHEBI:15422 (ChEBI)
Anionic phospholipids:microbial cell surfaceComplexR-ALL-8931784 (Reactome)
Anionic phospholipids MetaboliteCHEBI:62643 (ChEBI)
BPI ProteinP17213 (Uniprot-TrEMBL)
BPI:LPSComplexR-HSA-6807590 (Reactome)
BPIFA/BPIFB:bacterial cellComplexR-HSA-6809519 (Reactome)
BPIFA/BPIFBComplexR-HSA-6809283 (Reactome)
BPIFA1 ProteinQ9NP55 (Uniprot-TrEMBL)
BPIFA2 ProteinQ96DR5 (Uniprot-TrEMBL)
BPIFB1 ProteinQ8TDL5 (Uniprot-TrEMBL)
BPIFB2 ProteinQ8N4F0 (Uniprot-TrEMBL)
BPIFB4 ProteinP59827 (Uniprot-TrEMBL)
BPIFB6 ProteinQ8NFQ5 (Uniprot-TrEMBL)
BPIProteinP17213 (Uniprot-TrEMBL)
CAMP(134-170) ProteinP49913 (Uniprot-TrEMBL)
CAMP(134-170):microbial cell surfaceComplexR-HSA-8879163 (Reactome)
CAMP(134-170)ProteinP49913 (Uniprot-TrEMBL)
CAMP(31-170)ProteinP49913 (Uniprot-TrEMBL)
CHGA fragmentsComplexR-HSA-6808534 (Reactome)
CHGA(19-94) ProteinP10645 (Uniprot-TrEMBL)
CHGA(370-390) ProteinP10645 (Uniprot-TrEMBL)


anionic lipids
ComplexR-HSA-6808558 (Reactome)
CLU(228-449) ProteinP10909 (Uniprot-TrEMBL)
CLU(23-227) ProteinP10909 (Uniprot-TrEMBL)
CO3(2-) MetaboliteCHEBI:41609 (ChEBI)
CO3(2-)MetaboliteCHEBI:41609 (ChEBI)
CTSG ProteinP08311 (Uniprot-TrEMBL) After secretion Cathepsin G is extracellular and associated with the plasma membrane.
Ca2+ MetaboliteCHEBI:29108 (ChEBI)
Cu1+ MetaboliteCHEBI:49552 (ChEBI)
Cu1+MetaboliteCHEBI:49552 (ChEBI)
DCD hexamer:Zn(2+):anionic phospholipidsComplexR-HSA-6803105 (Reactome)
DCD peptidesComplexR-HSA-6803037 (Reactome)
DCD(20-110)ProteinP81605 (Uniprot-TrEMBL)
DCD(20-62)ProteinP81605 (Uniprot-TrEMBL)
DCD(63-109) ProteinP81605 (Uniprot-TrEMBL)
DCD(63-109)ProteinP81605 (Uniprot-TrEMBL)
DCD(63-110) ProteinP81605 (Uniprot-TrEMBL)
DCD(63-110):anionic phospholipidComplexR-HSA-6803024 (Reactome)
DCD(63-110)ProteinP81605 (Uniprot-TrEMBL)
DCD:anionic phospholipidComplexR-HSA-6803066 (Reactome)
DefensinsPathwayR-HSA-1461973 (Reactome) The 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.
In solution most alpha and beta defensins are monomers but can form dimers and higher order structures.

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.

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).

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).
Divalent metals

transported by

ComplexR-ALL-445829 (Reactome)
Divalent metals

transported by

ComplexR-ALL-445832 (Reactome)
ELANE ProteinP08246 (Uniprot-TrEMBL)
ELANE, CTSG, PRTN3ComplexR-HSA-6813639 (Reactome)


cell surface
ComplexR-HSA-6813664 (Reactome)
EPC:bacterial surfaceComplexR-HSA-6810673 (Reactome)
EPPIN:SEMG1:LTF:CLUComplexR-HSA-6810613 (Reactome)
Fe2+ MetaboliteCHEBI:18248 (ChEBI)
Fe3+ MetaboliteCHEBI:29034 (ChEBI)
Fe3+MetaboliteCHEBI:29034 (ChEBI)
GNLY ProteinP22749 (Uniprot-TrEMBL)
GNLY:bacterial anionic lipidsComplexR-HSA-6806759 (Reactome)
GNLY:bacterial anionic lipidsComplexR-HSA-8858201 (Reactome)
GNLYProteinP22749 (Uniprot-TrEMBL)
GlcNAc(1-->4)MurNAc:L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 R-ALL-6788957 (Reactome)
GlcNac-(1-->4)MurNAc-L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2 MetaboliteCHEBI:55424 (ChEBI) In Staphylococcus aureus, the pentapeptide coming off the N-acetyl muramic acid is composed of the amino acids L-alanine, D-glutamine, L-lysine, and two D-alanines.
GlcNac-(1-->4)MurNAc-L-Ala-gamma-D-Glu-L-Lys-(D-Ala)2MetaboliteCHEBI:55424 (ChEBI) In Staphylococcus aureus, the pentapeptide coming off the N-acetyl muramic acid is composed of the amino acids L-alanine, D-glutamine, L-lysine, and two D-alanines.
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HTN1 ProteinP15515 (Uniprot-TrEMBL)
HTN1(31-57) ProteinP15515 (Uniprot-TrEMBL)
HTN1,3,5:bacterial phospholipidsComplexR-HSA-6807169 (Reactome)
HTN1,3,5ComplexR-HSA-6807193 (Reactome)
HTN3 ProteinP15516 (Uniprot-TrEMBL)
HTN3(20-43) ProteinP15516 (Uniprot-TrEMBL)
HTN5, (HTN1, HTN3):SSA1,SSA2ComplexR-HSA-6807587 (Reactome)
HTN5,(HTN1, HTN3)ComplexR-HSA-6807573 (Reactome)
INTL1 ligandsComplexR-ALL-6804535 (Reactome)
INTL1:bacterial glycanComplexR-HSA-6804513 (Reactome)
ITLN1 ProteinQ8WWA0 (Uniprot-TrEMBL)
ITLN1 trimer:Ca2+ComplexR-HSA-6804509 (Reactome)
KDO MetaboliteCHEBI:85986 (ChEBI)
L-Ala-gamma-D-Glu-L-Lys-D-AlaMetaboliteCHEBI:61626 (ChEBI)
LCN2 ProteinP80188 (Uniprot-TrEMBL)
LCN2:2,5DHBA:Fe3+ComplexR-HSA-5229238 (Reactome)
LCN2:2,5DHBAComplexR-HSA-5229290 (Reactome)
LEAP2 ProteinQ969E1 (Uniprot-TrEMBL)
LEAP2:bacterial phospholipidsComplexR-HSA-6813633 (Reactome)
LEAP2ProteinQ969E1 (Uniprot-TrEMBL)
LPS MetaboliteCHEBI:16412 (ChEBI)
LPS, PGNComplexR-ALL-6803074 (Reactome)
LPSMetaboliteCHEBI:16412 (ChEBI)
LTF ProteinP02788 (Uniprot-TrEMBL)
LTF:2xFe3+:2xCO3(2-)ComplexR-HSA-1222432 (Reactome)
LTFProteinP02788 (Uniprot-TrEMBL)
LYZ ProteinP61626 (Uniprot-TrEMBL)
LYZ:PGNComplexR-HSA-8862293 (Reactome)
LYZProteinP61626 (Uniprot-TrEMBL)
Microbial cell surfaceR-ALL-8879165 (Reactome) This entity is intended to represent any molecule that might be at the outer cell surface of a microbial cell
Microbial cell surface R-ALL-8879165 (Reactome) This entity is intended to represent any molecule that might be at the outer cell surface of a microbial cell
Mn2+ MetaboliteCHEBI:29035 (ChEBI)
Mn2+MetaboliteCHEBI:29035 (ChEBI)
MurNAc MetaboliteCHEBI:21615 (ChEBI)
MurNAc:PeptideComplexR-ALL-6788991 (Reactome)
Na+ MetaboliteCHEBI:29101 (ChEBI)
Na+MetaboliteCHEBI:29101 (ChEBI)
PDZD11 ProteinQ5EBL8 (Uniprot-TrEMBL)
PGLYRP1 ProteinO75594 (Uniprot-TrEMBL)
PGLYRP1 dimerComplexR-HSA-6789200 (Reactome)
PGLYRP1dimer:peptidoglycanComplexR-HSA-6789175 (Reactome)
PGLYRP2 ProteinQ96PD5 (Uniprot-TrEMBL)
PGLYRP2 dimerComplexR-HSA-8933468 (Reactome)
PGLYRP2:peptidoglycanComplexR-HSA-6799988 (Reactome)
PGLYRP3 ProteinQ96LB9 (Uniprot-TrEMBL)
PGLYRP3,4 dimer:peptidoglycanComplexR-HSA-6799966 (Reactome)
PGLYRP3,4 dimersComplexR-HSA-6799960 (Reactome)
PGLYRP4 ProteinQ96LB8 (Uniprot-TrEMBL)
PI3(23-117) ProteinP19957 (Uniprot-TrEMBL)
PI3(61-117) ProteinP19957 (Uniprot-TrEMBL)
PI3:LPSComplexR-HSA-6810759 (Reactome)
PI3ComplexR-HSA-6810794 (Reactome)
PLA2G2A ProteinP14555 (Uniprot-TrEMBL)
PLA2G2A:Ca2+ComplexR-HSA-1602363 (Reactome)
PLA2G2A:phospholipidsComplexR-HSA-8862769 (Reactome)
PRSS2(24-247) ProteinP07478 (Uniprot-TrEMBL)
PRSS3 ProteinP35030 (Uniprot-TrEMBL)
PRTN3 ProteinP24158 (Uniprot-TrEMBL)
PRTN3ProteinP24158 (Uniprot-TrEMBL)
Peptide MetaboliteCHEBI:16670 (ChEBI)
PiMetaboliteCHEBI:18367 (ChEBI)


ComplexR-HSA-6801795 (Reactome)
REG3A(27-175) ProteinQ06141 (Uniprot-TrEMBL)
REG3A(27-175)/REG3G(27-175)ComplexR-HSA-6801779 (Reactome)
REG3A(27-37) ProteinQ06141 (Uniprot-TrEMBL)
REG3A(27-37)/REG3G(27-37)ComplexR-HSA-6801797 (Reactome)
REG3A(38-175) ProteinQ06141 (Uniprot-TrEMBL)
REG3A(38-175), REG3G(38-175):peptidoglycanComplexR-HSA-6801809 (Reactome)
REG3A(38-175), REG3G(38-175)ComplexR-HSA-6801794 (Reactome)
REG3A(38-175):anionic phospholipidsComplexR-HSA-6801804 (Reactome)
REG3A(38-175)ProteinQ06141 (Uniprot-TrEMBL)
REG3G(27-175) ProteinQ6UW15 (Uniprot-TrEMBL)
REG3G(27-37) ProteinQ6UW15 (Uniprot-TrEMBL)
REG3G(38-175) ProteinQ6UW15 (Uniprot-TrEMBL)
RNASE3 ProteinP12724 (Uniprot-TrEMBL)
RNASE3,RNASE7,RNASE6,(RNASE8)ComplexR-HSA-6803116 (Reactome)
RNASE6 ProteinQ93091 (Uniprot-TrEMBL)
RNASE7 ProteinQ9H1E1 (Uniprot-TrEMBL)
RNASE8 ProteinQ8TDE3 (Uniprot-TrEMBL)
RNASEs 3,6,7,(8):LPS,PGNComplexR-HSA-6803051 (Reactome)


ComplexR-HSA-8948028 (Reactome)
S100A7 ProteinP31151 (Uniprot-TrEMBL)
S100A7, S100A7A:Ca2+:Zn2+ComplexR-HSA-6798500 (Reactome)
S100A7, S100A7A:Ca2+ComplexR-HSA-6798557 (Reactome)
S100A7A ProteinQ86SG5 (Uniprot-TrEMBL)
S100A8 ProteinP05109 (Uniprot-TrEMBL)
S100A8:S100A9:Ca2+:Mn2+:Na+ComplexR-HSA-6798411 (Reactome)
S100A8:S100A9:Ca2+:Zn2+ComplexR-HSA-8944189 (Reactome)
S100A8:S100A9:Ca2+ComplexR-HSA-8944198 (Reactome)
S100A9 ProteinP06702 (Uniprot-TrEMBL)
SLC11A1ProteinP49279 (Uniprot-TrEMBL)
SSA1 ProteinP41797 (Uniprot-TrEMBL)
SSA1,SSA2ComplexR-CAL-6807575 (Reactome)
SSA2 ProteinP46587 (Uniprot-TrEMBL)
Trypsin 2, 3ComplexR-HSA-1460242 (Reactome)
Zn2+ MetaboliteCHEBI:29105 (ChEBI)