ID CAMP_HUMAN Reviewed; 170 AA. AC P49913; Q71SN9; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=Cathelicidin antimicrobial peptide {ECO:0000312|HGNC:HGNC:1472}; DE AltName: Full=18 kDa cationic antimicrobial protein {ECO:0000303|PubMed:7615076}; DE Short=CAP-18 {ECO:0000303|PubMed:7615076}; DE Short=hCAP-18 {ECO:0000303|PubMed:7615076}; DE Contains: DE RecName: Full=Antibacterial peptide FALL-39 {ECO:0000303|PubMed:7529412}; DE AltName: Full=FALL-39 peptide antibiotic {ECO:0000303|PubMed:7529412}; DE Contains: DE RecName: Full=Antibacterial peptide LL-37 {ECO:0000303|PubMed:8681941}; DE Contains: DE RecName: Full=Antibacterial peptide KR-20 {ECO:0000303|PubMed:14978112}; DE Contains: DE RecName: Full=Antibacterial peptide LL-23 {ECO:0000303|PubMed:14978112}; DE Contains: DE RecName: Full=Antibacterial peptide LL-29 {ECO:0000303|PubMed:14978112}; DE Contains: DE RecName: Full=Antibacterial peptide KS-30 {ECO:0000303|PubMed:14978112}; DE Contains: DE RecName: Full=Antibacterial peptide RK-31 {ECO:0000303|PubMed:14978112}; DE Contains: DE RecName: Full=Antibacterial peptide FF-33 {ECO:0000303|PubMed:14978112}; DE Flags: Precursor; GN Name=CAMP {ECO:0000312|HGNC:HGNC:1472}; GN Synonyms=CAP18 {ECO:0000303|PubMed:8946956}, FALL39 GN {ECO:0000303|PubMed:7529412}; ORFNames=HSD26; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 132-170, FUNCTION, AND TISSUE RP SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=7529412; DOI=10.1073/pnas.92.1.195; RA Agerberth B., Gunne H., Odeberg J., Kogner P., Boman H.G., RA Gudmundsson G.H.; RT "FALL-39, a putative human peptide antibiotic, is cysteine-free and RT expressed in bone marrow and testis."; RL Proc. Natl. Acad. Sci. U.S.A. 92:195-199(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 42-68 AND 83-100, AND RP TISSUE SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=7615076; DOI=10.1016/0014-5793(95)00634-l; RA Cowland J.B., Johnsen A.H., Borregaard N.; RT "hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil RT specific granules."; RL FEBS Lett. 368:173-176(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=7890387; DOI=10.1128/iai.63.4.1291-1297.1995; RA Larrick J.W., Hirata M., Balint R.F., Lee J., Zhong J., Wright S.C.; RT "Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein."; RL Infect. Immun. 63:1291-1297(1995). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RX PubMed=8946956; DOI=10.1016/s0014-5793(96)01199-4; RA Larrick J.W., Lee J., Ma S., Li X., Francke U., Wright S.C., Balint R.F.; RT "Structural, functional analysis and localization of the human CAP18 RT gene."; RL FEBS Lett. 398:74-80(1996). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 134-143, FUNCTION, RP AND TISSUE SPECIFICITY. RX PubMed=8681941; DOI=10.1111/j.1432-1033.1996.0325z.x; RA Gudmundsson G.H., Agerberth B., Odeberg J., Bergman T., Olsson B., RA Salcedo R.; RT "The human gene FALL39 and processing of the cathelin precursor to the RT antibacterial peptide LL-37 in granulocytes."; RL Eur. J. Biochem. 238:325-332(1996). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Epididymis; RA Gao Y., Huang Y.F., Xia X.Y.; RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RA Wu N., Miao S.Y., Zhang X.D., Qiao Y., Liang G., Wang L.F.; RT "A new spermatogenesis-related gene."; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=11238224; DOI=10.1128/cdli.8.2.370-375.2001; RA Bals R., Lang C., Weiner D.J., Vogelmeier C., Welsch U., Wilson J.M.; RT "Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close RT homologues of human molecules."; RL Clin. Diagn. Lab. Immunol. 8:370-375(2001). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND PHARMACEUTICAL. RX PubMed=9736536; DOI=10.1128/aac.42.9.2206; RA Turner J., Cho Y., Dinh N.N., Waring A.J., Lehrer R.I.; RT "Activities of LL-37, a cathelin-associated antimicrobial peptide of human RT neutrophils."; RL Antimicrob. Agents Chemother. 42:2206-2214(1998). RN [12] RP FUNCTION, SUBUNIT, PROTEOLYTIC CLEAVAGE, AND SYNTHESIS OF 134-170. RX PubMed=10417311; DOI=10.1042/bj3410501; RA Oren Z., Lerman J.C., Gudmundsson G.H., Agerberth B., Shai Y.; RT "Structure and organization of the human antimicrobial peptide LL-37 in RT phospholipid membranes: relevance to the molecular basis for its non-cell- RT selective activity."; RL Biochem. J. 341:501-513(1999). RN [13] RP TISSUE SPECIFICITY, PROTEOLYTIC CLEAVAGE, AND FUNCTION. RX PubMed=11389039; DOI=10.1182/blood.v97.12.3951; RA Soerensen O.E., Follin P., Johnsen A.H., Calafat J., Tjabringa G.S., RA Hiemstra P.S., Borregaard N.; RT "Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL- RT 37 by extracellular cleavage with proteinase 3."; RL Blood 97:3951-3959(2001). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PROTEOLYTIC RP CLEAVAGE. RX PubMed=14978112; DOI=10.4049/jimmunol.172.5.3070; RA Murakami M., Lopez-Garcia B., Braff M., Dorschner R.A., Gallo R.L.; RT "Postsecretory processing generates multiple cathelicidins for enhanced RT topical antimicrobial defense."; RL J. Immunol. 172:3070-3077(2004). RN [15] RP FUNCTION. RX PubMed=15778390; DOI=10.4049/jimmunol.174.7.4271; RA Braff M.H., Hawkins M.A., Di Nardo A., Lopez-Garcia B., Howell M.D., RA Wong C., Lin K., Streib J.E., Dorschner R., Leung D.Y., Gallo R.L.; RT "Structure-function relationships among human cathelicidin peptides: RT dissociation of antimicrobial properties from host immunostimulatory RT activities."; RL J. Immunol. 174:4271-4278(2005). RN [16] RP SYNTHESIS OF 134-170, AND FUNCTION. RX PubMed=21463582; DOI=10.1016/j.bpj.2011.02.018; RA Lee C.C., Sun Y., Qian S., Huang H.W.; RT "Transmembrane pores formed by human antimicrobial peptide LL-37."; RL Biophys. J. 100:1688-1696(2011). RN [17] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=22879591; DOI=10.1074/jbc.m112.394452; RA Woloszynek J.C., Hu Y., Pham C.T.; RT "Cathepsin G-regulated release of formyl peptide receptor agonists modulate RT neutrophil effector functions."; RL J. Biol. Chem. 287:34101-34109(2012). RN [18] RP FUNCTION, AND SYNTHESIS OF 134-170. RX PubMed=34708076; DOI=10.3389/fmolb.2021.742023; RA Zsila F., Ricci M., Szigyarto I.C., Singh P., Beke-Somfai T.; RT "Quorum Sensing Pseudomonas Quinolone Signal Forms Chiral Supramolecular RT Assemblies With the Host Defense Peptide LL-37."; RL Front. Mol. Biosci. 8:742023-742023(2021). RN [19] {ECO:0007744|PDB:2FBS, ECO:0007744|PDB:2FBU, ECO:0007744|PDB:2FCG} RP STRUCTURE BY NMR OF 146-170, AND FUNCTION. RX PubMed=16637646; DOI=10.1021/ja0584875; RA Li X., Li Y., Han H., Miller D.W., Wang G.; RT "Solution structures of human LL-37 fragments and NMR-based identification RT of a minimal membrane-targeting antimicrobial and anticancer region."; RL J. Am. Chem. Soc. 128:5776-5785(2006). RN [20] {ECO:0007744|PDB:2K6O} RP STRUCTURE BY NMR OF 134-170, AND FUNCTION. RX PubMed=18818205; DOI=10.1074/jbc.m805533200; RA Wang G.; RT "Structures of human host defense cathelicidin LL-37 and its smallest RT antimicrobial peptide KR-12 in lipid micelles."; RL J. Biol. Chem. 283:32637-32643(2008). RN [21] {ECO:0007744|PDB:2LMF} RP STRUCTURE BY NMR OF 134-156, PTM, AND MUTAGENESIS OF SER-142. RX PubMed=22185690; DOI=10.1021/bi2016266; RA Wang G., Elliott M., Cogen A.L., Ezell E.L., Gallo R.L., Hancock R.E.; RT "Structure, dynamics, and antimicrobial and immune modulatory activities of RT human LL-23 and its single-residue variants mutated on the basis of RT homologous primate cathelicidins."; RL Biochemistry 51:653-664(2012). RN [22] {ECO:0007744|PDB:4EYC} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 31-133, FUNCTION, DISULFIDE RP BONDS, MASS SPECTROMETRY, AND DOMAIN. RX PubMed=23406372; DOI=10.1021/bi301008r; RA Pazgier M., Ericksen B., Ling M., Toth E., Shi J., Li X., RA Galliher-Beckley A., Lan L., Zou G., Zhan C., Yuan W., Pozharski E., Lu W.; RT "Structural and functional analysis of the pro-domain of human RT cathelicidin, LL-37."; RL Biochemistry 52:1547-1558(2013). RN [23] {ECO:0007744|PDB:2NA3} RP STRUCTURE BY NMR OF 151-162. RA Gunasekera S., Muhammad T., Stromstedt A.A., Rosengren K.J., Goransson U.; RT "Backbone-cyclized stable peptide-dimers derived from the human RT cathelicidin LL-37 mediate potent antimicrobial activity."; RL Submitted (DEC-2015) to the PDB data bank. RN [24] {ECO:0007744|PDB:5XNG, ECO:0007744|PDB:5XRX} RP STRUCTURE BY NMR OF 149-165. RX PubMed=29087182; DOI=10.1021/acsami.7b13714; RA Singh S., Datta A., Borro B.C., Davoudi M., Schmidtchen A., Bhunia A., RA Malmsten M.; RT "Conformational Aspects of High Content Packing of Antimicrobial Peptides RT in Polymer Microgels."; RL ACS Appl. Mater. Interfaces 9:40094-40106(2017). RN [25] {ECO:0007744|PDB:5NMN, ECO:0007744|PDB:5NNK, ECO:0007744|PDB:5NNM, ECO:0007744|PDB:5NNT} RP X-RAY CRYSTALLOGRAPHY (0.95 ANGSTROMS) OF 134-170, FUNCTION, AND SUBUNIT. RX PubMed=29133814; DOI=10.1038/s41598-017-14206-1; RA Sancho-Vaello E., Francois P., Bonetti E.J., Lilie H., Finger S., RA Gil-Ortiz F., Gil-Carton D., Zeth K.; RT "Structural remodeling and oligomerization of human cathelicidin on RT membranes suggest fibril-like structures as active species."; RL Sci. Rep. 7:15371-15371(2017). RN [26] {ECO:0007744|PDB:6BIV, ECO:0007744|PDB:6BIX} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF CITRULLINATED 83-95 IN COMPLEX RP WITH HLA-DRA AND HLA-DRB1. RX PubMed=29317506; DOI=10.1074/jbc.ra117.001013; RA Ting Y.T., Petersen J., Ramarathinam S.H., Scally S.W., Loh K.L., RA Thomas R., Suri A., Baker D.G., Purcell A.W., Reid H.H., Rossjohn J.; RT "The interplay between citrullination and HLA-DRB1 polymorphism in shaping RT peptide binding hierarchies in rheumatoid arthritis."; RL J. Biol. Chem. 293:3236-3251(2018). RN [27] {ECO:0007744|PDB:6S6M} RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 150-162, FUNCTION, DOMAIN, AND RP MUTAGENESIS OF PHE-150; LYS-151; GLN-155; ILE-157 AND PHE-160. RX PubMed=32753597; DOI=10.1038/s41467-020-17736-x; RA Engelberg Y., Landau M.; RT "The Human LL-37(17-29) antimicrobial peptide reveals a functional RT supramolecular structure."; RL Nat. Commun. 11:3894-3894(2020). RN [28] {ECO:0007744|PDB:7PDC} RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 134-170, FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF GLU-149 AND ARG-156. RX PubMed=33060695; DOI=10.1038/s41598-020-74401-5; RA Sancho-Vaello E., Gil-Carton D., Francois P., Bonetti E.J., Kreir M., RA Pothula K.R., Kleinekathofer U., Zeth K.; RT "The structure of the antimicrobial human cathelicidin LL-37 shows RT oligomerization and channel formation in the presence of membrane mimics."; RL Sci. Rep. 10:17356-17356(2020). RN [29] {ECO:0007744|PDB:7NPQ} RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 150-162 OF MUTANT CYS-153, AND RP DOMAIN. RX PubMed=35061360; DOI=10.1021/acs.biomac.1c01353; RA Engelberg Y., Ragonis-Bachar P., Landau M.; RT "Rare by Natural Selection: Disulfide-Bonded Supramolecular Antimicrobial RT Peptides."; RL Biomacromolecules 23:926-936(2022). CC -!- FUNCTION: Antimicrobial protein that is an integral component of the CC innate immune system (PubMed:22879591, PubMed:16637646, CC PubMed:18818205, PubMed:9736536, PubMed:14978112). Binds to bacterial CC lipopolysaccharides (LPS) (PubMed:16637646, PubMed:18818205). Acts via CC neutrophil N-formyl peptide receptors to enhance the release of CXCL2 CC (PubMed:22879591). Postsecretory processing generates multiple CC cathelicidin antimicrobial peptides with various lengths which act as a CC topical antimicrobial defense in sweat on skin (PubMed:14978112). The CC unprocessed precursor form, cathelicidin antimicrobial peptide, CC inhibits the growth of Gram-negative E.coli and E.aerogenes with CC efficiencies comparable to that of the mature peptide LL-37 (in vitro) CC (PubMed:9736536). {ECO:0000269|PubMed:14978112, CC ECO:0000269|PubMed:16637646, ECO:0000269|PubMed:18818205, CC ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:9736536}. CC -!- FUNCTION: [Antibacterial peptide LL-37]: Antimicrobial peptide that is CC an integral component of the innate immune system (PubMed:8681941, CC PubMed:9736536, PubMed:10417311, PubMed:15778390, PubMed:22879591, CC PubMed:34708076, PubMed:16637646, PubMed:18818205, PubMed:32753597, CC PubMed:33060695). Binds to bacterial lipopolysaccharides (LPS) CC (PubMed:16637646, PubMed:18818205, PubMed:9736536, PubMed:10417311, CC PubMed:33060695). Causes membrane permeabilization by forming CC transmembrane pores (in vitro) (PubMed:22879591, PubMed:32753597, CC PubMed:33060695). Causes lysis of E.coli (PubMed:10417311). Exhibits CC antimicrobial activity against Gram-negative bacteria such as CC P.aeruginosa, S.typhimurium, E.aerogenes, E.coli and P.syringae, Gram- CC positive bacteria such as L.monocytogenes, S.epidermidis, S.pyogenes CC and S.aureus, as well as vancomycin-resistant enterococci (in vitro) CC (PubMed:8681941, PubMed:9736536, PubMed:10417311, PubMed:32753597). CC Exhibits antimicrobial activity against methicillin-resistant S.aureus, CC P.mirabilis, and C.albicans in low-salt media, but not in media CC containing 100 mM NaCl (in vitro) (PubMed:9736536). Forms chiral CC supramolecular assemblies with quinolone signal (PQS) molecules of CC P.aeruginosa, which may lead to interference of bacterial quorum CC signaling and perturbance of bacterial biofilm formation CC (PubMed:34708076). May form supramolecular fiber-like assemblies on CC bacterial membranes (PubMed:29133814). Induces cytokine and chemokine CC production as well as TNF/TNFA and CSF2/GMCSF production in normal CC human keratinocytes (PubMed:15778390). Exhibits hemolytic activity CC against red blood cells (PubMed:10417311). CC {ECO:0000269|PubMed:10417311, ECO:0000269|PubMed:15778390, CC ECO:0000269|PubMed:16637646, ECO:0000269|PubMed:18818205, CC ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:29133814, CC ECO:0000269|PubMed:32753597, ECO:0000269|PubMed:33060695, CC ECO:0000269|PubMed:34708076, ECO:0000269|PubMed:8681941, CC ECO:0000269|PubMed:9736536}. CC -!- FUNCTION: [Antibacterial peptide FALL-39]: Exhibits antimicrobial CC activity against E.coli and B.megaterium (in vitro). CC {ECO:0000269|PubMed:7529412, ECO:0000269|PubMed:8681941}. CC -!- FUNCTION: [Antibacterial peptide KR-20]: Acts synergistically with CC peptides KS-30 and KR-31, killing bacteria such as S.aureus, E.coli and CC C.albicans at lower concentrations when present together, and maintains CC activity at increased salt condition (PubMed:14978112). Does not have CC the ability to stimulate CXCL8/IL8 release from keratinocytes CC (PubMed:14978112). {ECO:0000269|PubMed:14978112}. CC -!- FUNCTION: [Antibacterial peptide LL-23]: Poorly active (MIC > 150 uM) CC against E.coli strain K12 (PubMed:14978112). Is able to induce the pro- CC inflammatory cytokine TNF/TNFA or the chemokine CCL2/MCP1 CC (PubMed:14978112). {ECO:0000269|PubMed:14978112}. CC -!- FUNCTION: [Antibacterial peptide LL-29]: Moderately antibacterial. CC {ECO:0000269|PubMed:14978112}. CC -!- FUNCTION: [Antibacterial peptide KS-30]: Moderately antibacterial CC (PubMed:14978112). Acts synergistically with peptides KR-20 and KR-31, CC killing bacteria such as S.aureus, E.coli and C.albicans at lower CC concentrations when present together, and maintain activity at CC increased salt condition (PubMed:14978112). Does not have the ability CC to stimulate CXCL8/IL8 release from keratinocytes (PubMed:14978112). CC {ECO:0000269|PubMed:14978112}. CC -!- FUNCTION: [Antibacterial peptide RK-31]: Acts synergistically with CC peptides KS-30 and KR-31, killing bacteria such as S.aureus, E.coli and CC C.albicans at lower concentrations when present together, and maintain CC activity at increased salt condition (PubMed:14978112). Does not have CC the ability to stimulate CXCL8/IL8 release from keratinocytes CC (PubMed:14978112). {ECO:0000269|PubMed:14978112}. CC -!- FUNCTION: [Antibacterial peptide FF-33]: Inhibits the growth of E.coli CC and B.megaterium and exhibits hemolytic activity against human red CC blood cells. {ECO:0000269|PubMed:14978112}. CC -!- SUBUNIT: [Antibacterial peptide LL-37]: Monomer, homodimer or CC homotrimer (in vitro) (PubMed:10417311). Oligomerizes as tetra- or CC hexamer in solution (in vitro) (PubMed:10417311, PubMed:29133814, CC PubMed:32753597). {ECO:0000269|PubMed:10417311, CC ECO:0000269|PubMed:29133814, ECO:0000269|PubMed:32753597}. CC -!- INTERACTION: CC PRO_0000004724; P08069: IGF1R; NbExp=3; IntAct=EBI-6378485, EBI-475981; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:14978112}. Vesicle CC {ECO:0000269|PubMed:7529412, ECO:0000269|PubMed:9736536}. Note=Stored CC as pro-peptide in granules and phagolysosomes of neutrophils CC (PubMed:9736536, PubMed:7529412). Secreted in sweat onto skin CC (PubMed:14978112). {ECO:0000269|PubMed:14978112, CC ECO:0000269|PubMed:7529412, ECO:0000269|PubMed:9736536}. CC -!- TISSUE SPECIFICITY: Expressed in neutrophilic granulocytes (at protein CC level) (PubMed:7890387, PubMed:8946956, PubMed:9736536, PubMed:7529412, CC PubMed:7615076, PubMed:8681941). Expressed in bone marrow CC (PubMed:7890387). {ECO:0000269|PubMed:7529412, CC ECO:0000269|PubMed:7615076, ECO:0000269|PubMed:7890387, CC ECO:0000269|PubMed:8681941, ECO:0000269|PubMed:8946956, CC ECO:0000269|PubMed:9736536}. CC -!- TISSUE SPECIFICITY: [Antibacterial peptide LL-37]: Expressed in CC granulocytes (at protein level) (PubMed:8681941). Expressed by the CC eccrine apparatus and secreted into sweat on skin (at protein level) CC (PubMed:14978112). {ECO:0000269|PubMed:14978112, CC ECO:0000269|PubMed:8681941}. CC -!- TISSUE SPECIFICITY: [Antibacterial peptide FALL-39]: Expressed in bone CC marrow and testis. {ECO:0000269|PubMed:7529412}. CC -!- DOMAIN: The cathelin-like domain (CLD), which is the propeptide part, CC does not seem to exhibit auto-inhibitory function, as it does not CC inhibit the antibacterial activity of antibacterial peptide LL-37. CC {ECO:0000269|PubMed:23406372}. CC -!- DOMAIN: [Antibacterial peptide LL-37]: Undergoes conformational change CC in the presence of lipid A, transitioning from a random coil to an CC alpha-helical structure. {ECO:0000269|PubMed:9736536}. CC -!- DOMAIN: [Antibacterial peptide LL-37]: Residues 17-29 of LL-37 CC represent the active core of the antimicrobial peptide CC (PubMed:32753597, PubMed:35061360). Forms ribbon-like fibrils and CC exhibits antibacterial activity against Gram-positive M.luteus (MIC=22- CC 25 uM) and S.hominis (MIC=39 uM) (PubMed:32753597, PubMed:35061360). CC Also exhibits antibacterial activity against Gram-negative E.coli CC (MIC=47 uM) and P.fluorescens (MIC=136 uM) (PubMed:35061360). CC {ECO:0000269|PubMed:32753597, ECO:0000269|PubMed:35061360}. CC -!- PTM: The N-terminus is blocked. CC -!- PTM: Proteolytically cleaved by proteinase PRTN3 into antibacterial CC peptide LL-37 (PubMed:11389039). Proteolytically cleaved by cathepsin CC CTSG and neutrophil elastase ELANE (PubMed:22879591, PubMed:11389039). CC {ECO:0000269|PubMed:11389039, ECO:0000269|PubMed:22879591}. CC -!- PTM: [Antibacterial peptide LL-37]: Resistant to proteolytic CC degradation in solution, and when bound to both zwitterionic (mimicking CC mammalian membranes) and negatively charged membranes (mimicking CC bacterial membranes). {ECO:0000269|PubMed:10417311}. CC -!- PTM: After secretion onto the skin surface, the CAMP gene product is CC processed by a serine protease-dependent mechanism into multiple novel CC antimicrobial peptides distinct from and shorter than cathelicidin LL- CC 37, such as peptides KR-20 (residues 151-170), LL-23 (residues 134- CC 156), LL-29 (residues 134-162), KS-30 (residues 141-170), RK-31 CC (residues 140-170) and FF-33 (residues 138-170) (PubMed:14978112). The CC peptides act synergistically, killing bacteria at lower concentrations CC when present together, and maintain activity at increased salt CC condition (PubMed:14978112). {ECO:0000269|PubMed:14978112}. CC -!- MASS SPECTROMETRY: [Antibacterial peptide LL-37]: Mass=4492.9; CC Method=Electrospray; Evidence={ECO:0000269|PubMed:23406372}; CC -!- MASS SPECTROMETRY: Mass=16424.5; Method=Electrospray; Note=Precursor CC form pro-cathelicidin.; Evidence={ECO:0000269|PubMed:23406372}; CC -!- MASS SPECTROMETRY: Mass=11949.2; Method=Electrospray; Note=Propeptide CC Cathelin-like domain (CLD).; Evidence={ECO:0000269|PubMed:23406372}; CC -!- PHARMACEUTICAL: The potent activity of antibacterial peptide LL-37 CC against P.aeruginosa, including mucoid and antibiotic-resistant CC strains, suggests that the peptide or related molecules might have CC utility as topical bronchopulmonary microbicides in cystic fibrosis. CC {ECO:0000269|PubMed:9736536}. CC -!- MISCELLANEOUS: The propeptide shows high sequence homology to cathelin, CC a protein of 96 residues isolated from porcine neutrophils, and is CC therefore also named cathelin-like domain (CLD) (PubMed:9736536). CC Cathelin was initially classified into the cystatin family of cysteine CC protease inhibitors based on its inhibitory activity against cathepsin CC L (PubMed:9736536). Human CLD itself lacks antimicrobial function and CC does not inhibit the cysteine protease, cathepsin L (PubMed:9736536). CC {ECO:0000269|PubMed:9736536}. CC -!- SIMILARITY: Belongs to the cathelicidin family. {ECO:0000305}. CC -!- CAUTION: PubMed:11238224 sequence was incorrectly assigned to originate CC from M.mulatta. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z38026; CAA86115.1; -; mRNA. DR EMBL; X89658; CAA61805.1; -; mRNA. DR EMBL; U19970; AAA74084.1; -; mRNA. DR EMBL; U48795; AAC02634.1; -; Genomic_DNA. DR EMBL; X96735; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY162210; AAN78318.1; -; mRNA. DR EMBL; AY251531; AAP20054.1; -; mRNA. DR EMBL; AF288284; AAG40802.1; -; mRNA. DR EMBL; CR457083; CAG33364.1; -; mRNA. DR EMBL; CR541961; CAG46759.1; -; mRNA. DR EMBL; BC055089; AAH55089.1; -; mRNA. DR CCDS; CCDS2762.3; -. DR PIR; I38932; I38932. DR PIR; S74248; S74248. DR RefSeq; NP_004336.3; NM_004345.4. DR PDB; 2FBS; NMR; -; N=150-162. DR PDB; 2FBU; NMR; -; H=134-145. DR PDB; 2FCG; NMR; -; F=146-170. DR PDB; 2K6O; NMR; -; A=134-170. DR PDB; 2LMF; NMR; -; A=134-156. DR PDB; 2NA3; NMR; -; A=151-162. DR PDB; 4EYC; X-ray; 1.90 A; A/B=31-133. DR PDB; 5NMN; X-ray; 0.95 A; A=134-170. DR PDB; 5NNK; X-ray; 1.80 A; A=134-170. DR PDB; 5NNM; X-ray; 1.90 A; A/B=134-170. DR PDB; 5NNT; X-ray; 2.21 A; A/B=134-170. DR PDB; 5XNG; NMR; -; A=149-165. DR PDB; 5XRX; NMR; -; A=149-165. DR PDB; 6BIV; X-ray; 2.90 A; C=83-95. DR PDB; 6BIX; X-ray; 2.20 A; C=83-95. DR PDB; 6S6M; X-ray; 1.35 A; A/B=150-162. DR PDB; 7NPQ; X-ray; 1.50 A; A/B=150-162. DR PDB; 7PDC; X-ray; 1.83 A; A/B=134-170. DR PDB; 7SAY; X-ray; 2.10 A; E/F=134-170. DR PDB; 8DEW; EM; 2.89 A; D=150-165. DR PDBsum; 2FBS; -. DR PDBsum; 2FBU; -. DR PDBsum; 2FCG; -. DR PDBsum; 2K6O; -. DR PDBsum; 2LMF; -. DR PDBsum; 2NA3; -. DR PDBsum; 4EYC; -. DR PDBsum; 5NMN; -. DR PDBsum; 5NNK; -. DR PDBsum; 5NNM; -. DR PDBsum; 5NNT; -. DR PDBsum; 5XNG; -. DR PDBsum; 5XRX; -. DR PDBsum; 6BIV; -. DR PDBsum; 6BIX; -. DR PDBsum; 6S6M; -. DR PDBsum; 7NPQ; -. DR PDBsum; 7PDC; -. DR PDBsum; 7SAY; -. DR PDBsum; 8DEW; -. DR AlphaFoldDB; P49913; -. DR BMRB; P49913; -. DR EMDB; EMD-27401; -. DR SMR; P49913; -. DR BioGRID; 107270; 18. DR IntAct; P49913; 2. DR STRING; 9606.ENSP00000296435; -. DR DrugBank; DB02345; Selenocysteine. DR TCDB; 1.C.33.1.10; the cathelicidin (cathelicidin) family. DR GlyCosmos; P49913; 1 site, 2 glycans. DR GlyGen; P49913; 1 site, 2 O-linked glycans (1 site). DR iPTMnet; P49913; -. DR PhosphoSitePlus; P49913; -. DR BioMuta; CAMP; -. DR DMDM; 1706745; -. DR jPOST; P49913; -. DR MassIVE; P49913; -. DR PaxDb; 9606-ENSP00000296435; -. DR PeptideAtlas; P49913; -. DR ProteomicsDB; 56178; -. DR Pumba; P49913; -. DR ABCD; P49913; 13 sequenced antibodies. DR Antibodypedia; 13077; 515 antibodies from 35 providers. DR DNASU; 820; -. DR Ensembl; ENST00000652295.2; ENSP00000498425.1; ENSG00000164047.6. DR GeneID; 820; -. DR KEGG; hsa:820; -. DR MANE-Select; ENST00000652295.2; ENSP00000498425.1; NM_004345.5; NP_004336.4. DR AGR; HGNC:1472; -. DR CTD; 820; -. DR DisGeNET; 820; -. DR GeneCards; CAMP; -. DR HGNC; HGNC:1472; CAMP. DR HPA; ENSG00000164047; Tissue enriched (bone). DR MIM; 600474; gene. DR neXtProt; NX_P49913; -. DR OpenTargets; ENSG00000164047; -. DR PharmGKB; PA26054; -. DR VEuPathDB; HostDB:ENSG00000164047; -. DR eggNOG; ENOG502SAES; Eukaryota. DR GeneTree; ENSGT00390000000410; -. DR InParanoid; P49913; -. DR OrthoDB; 4210525at2759; -. DR PhylomeDB; P49913; -. DR TreeFam; TF338457; -. DR BioCyc; MetaCyc:ENSG00000164047-MONOMER; -. DR PathwayCommons; P49913; -. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-6803157; Antimicrobial peptides. DR SignaLink; P49913; -. DR SIGNOR; P49913; -. DR BioGRID-ORCS; 820; 13 hits in 1147 CRISPR screens. DR EvolutionaryTrace; P49913; -. DR GeneWiki; Cathelicidin; -. DR GenomeRNAi; 820; -. DR Pharos; P49913; Tbio. DR PRO; PR:P49913; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P49913; Protein. DR Bgee; ENSG00000164047; Expressed in trabecular bone tissue and 117 other cell types or tissues. DR ExpressionAtlas; P49913; baseline and differential. DR GO; GO:0042995; C:cell projection; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0042581; C:specific granule; IDA:UniProtKB. DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome. DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome. DR GO; GO:0001530; F:lipopolysaccharide binding; IBA:GO_Central. DR GO; GO:1990000; P:amyloid fibril formation; IDA:DisProt. DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB. DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0071354; P:cellular response to interleukin-6; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071224; P:cellular response to peptidoglycan; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0019835; P:cytolysis; EXP:DisProt. DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IBA:GO_Central. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB. DR GO; GO:0045087; P:innate immune response; IBA:GO_Central. DR GO; GO:0002227; P:innate immune response in mucosa; IDA:UniProtKB. DR GO; GO:0051873; P:killing by host of symbiont cells; IDA:CACAO. DR GO; GO:0042119; P:neutrophil activation; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl. DR DisProt; DP00004; -. DR Gene3D; 3.10.450.10; -; 1. DR InterPro; IPR001894; Cathelicidin-like. DR InterPro; IPR018216; Cathelicidin_CS. DR InterPro; IPR022746; Cathlecidin_C. DR InterPro; IPR046350; Cystatin_sf. DR PANTHER; PTHR10206; CATHELICIDIN; 1. DR PANTHER; PTHR10206:SF2; CATHELICIDIN ANTIMICROBIAL PEPTIDE; 1. DR Pfam; PF12153; CAP18_C; 1. DR Pfam; PF00666; Cathelicidins; 1. DR SUPFAM; SSF54403; Cystatin/monellin; 1. DR PROSITE; PS00946; CATHELICIDINS_1; 1. DR PROSITE; PS00947; CATHELICIDINS_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic; Antimicrobial; KW Cleavage on pair of basic residues; Direct protein sequencing; KW Disulfide bond; Immunity; Innate immunity; Pharmaceutical; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..30 FT /evidence="ECO:0000255" FT PROPEP 31..131 FT /note="Cathelin-like domain (CLD)" FT /evidence="ECO:0000269|PubMed:7615076, FT ECO:0000303|PubMed:9736536" FT /id="PRO_0000004722" FT PEPTIDE 132..170 FT /note="Antibacterial peptide FALL-39" FT /evidence="ECO:0000269|PubMed:7529412" FT /id="PRO_0000004723" FT PEPTIDE 134..170 FT /note="Antibacterial peptide LL-37" FT /evidence="ECO:0000269|PubMed:8681941" FT /id="PRO_0000004724" FT PEPTIDE 134..162 FT /note="Antibacterial peptide LL-29" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456769" FT PEPTIDE 134..156 FT /note="Antibacterial peptide LL-23" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456768" FT PEPTIDE 138..170 FT /note="Antibacterial peptide FF-33" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456772" FT PEPTIDE 140..170 FT /note="Antibacterial peptide RK-31" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456771" FT PEPTIDE 141..170 FT /note="Antibacterial peptide KS-30" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456770" FT PEPTIDE 151..170 FT /note="Antibacterial peptide KR-20" FT /evidence="ECO:0000269|PubMed:14978112" FT /id="PRO_0000456767" FT REGION 150..162 FT /note="Active core" FT /evidence="ECO:0000269|PubMed:32753597" FT DISULFID 86..97 FT /evidence="ECO:0000269|PubMed:23406372, FT ECO:0007744|PDB:4EYC" FT DISULFID 108..125 FT /evidence="ECO:0000269|PubMed:23406372, FT ECO:0007744|PDB:4EYC" FT MUTAGEN 142 FT /note="S->A: Slightly increased MIC against E.coli K12 FT (MIC=15 compared to MIC=5)." FT /evidence="ECO:0000269|PubMed:22185690" FT MUTAGEN 142 FT /note="S->V: Slightly increased MIC against E.coli K12 FT (MIC=25 compared to MIC=5)." FT /evidence="ECO:0000269|PubMed:22185690" FT MUTAGEN 149 FT /note="E->A: Disrupts oligomerization. Loss of FT antimicrobial activity." FT /evidence="ECO:0000269|PubMed:33060695" FT MUTAGEN 150 FT /note="F->A: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 150 FT /note="F->S: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 151 FT /note="K->A: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 151 FT /note="K->H: Reduced antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 151 FT /note="K->Q: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 151 FT /note="K->R: No impact on antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 155 FT /note="Q->A: No impact on antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 156 FT /note="R->A: Impacts oligomerization. Loss of antimicrobial FT activity." FT /evidence="ECO:0000269|PubMed:33060695" FT MUTAGEN 157 FT /note="I->A: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 157 FT /note="I->D: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 157 FT /note="I->K: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 157 FT /note="I->Q: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 157 FT /note="I->S: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT MUTAGEN 160 FT /note="F->A: Loss of antimicrobial activity against FT M.luteus." FT /evidence="ECO:0000269|PubMed:32753597" FT CONFLICT 6 FT /note="D -> N (in Ref. 1, 6, 7 and 9; CAG46759)" FT /evidence="ECO:0000305" FT HELIX 35..49 FT /evidence="ECO:0007829|PDB:4EYC" FT STRAND 53..61 FT /evidence="ECO:0007829|PDB:4EYC" FT STRAND 75..87 FT /evidence="ECO:0007829|PDB:4EYC" FT HELIX 94..96 FT /evidence="ECO:0007829|PDB:4EYC" FT STRAND 105..112 FT /evidence="ECO:0007829|PDB:4EYC" FT STRAND 122..126 FT /evidence="ECO:0007829|PDB:4EYC" FT HELIX 135..163 FT /evidence="ECO:0007829|PDB:5NMN" SQ SEQUENCE 170 AA; 19301 MW; 055B07DCA95A7D16 CRC64; MKTQRDGHSL GRWSLVLLLL GLVMPLAIIA QVLSYKEAVL RAIDGINQRS SDANLYRLLD LDPRPTMDGD PDTPKPVSFT VKETVCPRTT QQSPEDCDFK KDGLVKRCMG TVTLNQARGS FDISCDKDNK RFALLGDFFR KSKEKIGKEF KRIVQRIKDF LRNLVPRTES //