Cathelicidin

Cathelicidin

Crystal Structure Analysis of the Cathelicidin Motif of Protegrins
Identifiers
Symbol	Cathelicidin
Pfam	PF00666
Pfam clan	CL0121
InterPro	IPR001894
PROSITE	PDOC00729
SCOP	1lyp
SUPERFAMILY	1lyp
OPM family	236
OPM protein	2k6o
Available protein structures: Pfam structures PDB RCSB PDB; PDBe PDBsum structure summary

Cathelicidin antimicrobial peptide
Rendering based on PDB 2FBS.
Available structures PDB 2FBS, 2FBU, 2FCG, 2K6O
Identifiers
Symbols	CAMP; CAP-18; CAP18; CRAMP; FALL-39; FALL39; LL37
External IDs	OMIM: 600474 MGI: 108443 HomoloGene: 110678 GeneCards: CAMP Gene
Gene Ontology Cellular component • extracellular region • specific granule Biological process • defense response to bacterium • negative regulation of growth of symbiont in host • negative regulation of growth of symbiont on or near host surface • defense response to Gram-negative bacterium • defense response to Gram-positive bacterium • killing by host of symbiont cells Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	820	12796
Ensembl	ENSG00000164047	ENSMUSG00000038357
UniProt	P49913	Q0VB78
RefSeq (mRNA)	NM_004345.3	NM_009921.2
RefSeq (protein)	NP_004336.2	NP_034051.2
Location (UCSC)	Chr 3: 48.26 – 48.27 Mb	Chr 9: 109.75 – 109.75 Mb
PubMed search	[1]	[2]

Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes in macrophages and polymorphonuclear leukocytes (PMNs). Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection.

Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.^{[citation needed]}

Cathelicidin peptides have been isolated from many different species of mammals. Cathelicidins were originally found in neutrophils but have since been found in many other cells including epithelial cells and macrophages after activation by bacteria, viruses, fungi, or the hormone 1,25-D, which is the hormonally active form of vitamin D.

The cathelicidin family shares primary sequence homology with the cystatin family of cysteine proteinase inhibitors, although amino acid residues thought to be important in such protease inhibition are usually lacking.

Family members

• Cathelicidin
• LL-37
• porcine PR-39
• human FALL-39
• hCAP-18
• CRAMP-1/2, Cathelin-related Antimicrobial Peptide

Clinical significance

Patients with rosacea have elevated levels of cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Antibiotics have been used in the past to treat rosacea, but antibiotics may only work because they inhibit some SCTEs.

Higher levels of human cathelicidin antimicrobial protein (hCAP18), which are regulated by vitamin D, appear to significantly reduce the risk of death from infection in dialysis patients. Patients with a high level of this protein were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection.

See also

• Antimicrobial peptides
• Innate immune system

Further reading

• Dürr UH, Sudheendra US, Ramamoorthy A (September 2006). "LL-37, the only human member of the cathelicidin family of antimicrobial peptides". Biochim. Biophys. Acta 1758 (9): 1408–25. doi:10.1016/j.bbamem.2006.03.030. PMID 16716248. 
• Chromek M, Slamová Z, Bergman P, Kovács L, Podracká L, Ehrén I, Hökfelt T, Gudmundsson GH, Gallo RL, Agerberth B, Brauner A (June 2006). "The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection". Nat. Med. 12 (6): 636–41. doi:10.1038/nm1407. PMID 16751768. 
• Gombart AF, Borregaard N, Koeffler HP (July 2005). "Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3". FASEB J. 19 (9): 1067–77. doi:10.1096/fj.04-3284com. PMID 15985530. 
• López-García B, Lee PH, Gallo RL (May 2006). "Expression and potential function of cathelicidin antimicrobial peptides in dermatophytosis and tinea versicolor". J. Antimicrob. Chemother. 57 (5): 877–82. doi:10.1093/jac/dkl078. PMID 16556635. 
• Lehrer RI, Ganz T (2002). "Cathelicidins: a family of endogenous antimicrobial peptides.". Curr. Opin. Hematol. 9 (1): 18–22. doi:10.1097/00062752-200201000-00004. PMID 11753073. 
• Niyonsaba F, Hirata M, Ogawa H, Nagaoka I (2003). "Epithelial cell-derived antibacterial peptides human beta-defensins and cathelicidin: multifunctional activities on mast cells.". Current drug targets. Inflammation and allergy 2 (3): 224–31. doi:10.2174/1568010033484115. PMID 14561157. 
• van Wetering S, Tjabringa GS, Hiemstra PS (2005). "Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells.". J. Leukoc. Biol. 77 (4): 444–50. doi:10.1189/jlb.0604367. PMID 15591123. 
• Agerberth B, Gunne H, Odeberg J, et al. (1995). "FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis.". Proc. Natl. Acad. Sci. U.S.A. 92 (1): 195–9. doi:10.1073/pnas.92.1.195. PMC 42844. PMID 7529412. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=42844. 
• Cowland JB, Johnsen AH, Borregaard N (1995). "hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules.". FEBS Lett. 368 (1): 173–6. doi:10.1016/0014-5793(95)00634-L. PMID 7615076. 
• Gudmundsson GH, Magnusson KP, Chowdhary BP, et al. (1995). "Structure of the gene for porcine peptide antibiotic PR-39, a cathelin gene family member: comparative mapping of the locus for the human peptide antibiotic FALL-39.". Proc. Natl. Acad. Sci. U.S.A. 92 (15): 7085–9. doi:10.1073/pnas.92.15.7085. PMC 41476. PMID 7624374. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=41476. 
• Larrick JW, Hirata M, Balint RF, et al. (1995). "Human CAP18: a novel antimicrobial lipopolysaccharide-binding protein.". Infect. Immun. 63 (4): 1291–7. PMC 173149. PMID 7890387. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=173149. 
• Gudmundsson GH, Agerberth B, Odeberg J, et al. (1996). "The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL-37 in granulocytes.". Eur. J. Biochem. 238 (2): 325–32. doi:10.1111/j.1432-1033.1996.0325z.x. PMID 8681941. 
• Larrick JW, Lee J, Ma S, et al. (1997). "Structural, functional analysis and localization of the human CAP18 gene.". FEBS Lett. 398 (1): 74–80. doi:10.1016/S0014-5793(96)01199-4. PMID 8946956. 
• Frohm M, Agerberth B, Ahangari G, et al. (1997). "The expression of the gene coding for the antibacterial peptide LL-37 is induced in human keratinocytes during inflammatory disorders.". J. Biol. Chem. 272 (24): 15258–63. doi:10.1074/jbc.272.24.15258. PMID 9182550. 
• Bals R, Wang X, Zasloff M, Wilson JM (1998). "The peptide antibiotic LL-37/hCAP-18 is expressed in epithelia of the human lung where it has broad antimicrobial activity at the airway surface.". Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9541–6. doi:10.1073/pnas.95.16.9541. PMC 21374. PMID 9689116. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21374. 
• Frohm Nilsson M, Sandstedt B, Sørensen O, et al. (1999). "The human cationic antimicrobial protein (hCAP18), a peptide antibiotic, is widely expressed in human squamous epithelia and colocalizes with interleukin-6.". Infect. Immun. 67 (5): 2561–6. PMC 116004. PMID 10225921. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=116004. 
• Malm J, Sørensen O, Persson T, et al. (2000). "The human cationic antimicrobial protein (hCAP-18) is expressed in the epithelium of human epididymis, is present in seminal plasma at high concentrations, and is attached to spermatozoa.". Infect. Immun. 68 (7): 4297–302. doi:10.1128/IAI.68.7.4297-4302.2000. PMC 101750. PMID 10858248. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=101750. 
• Sørensen OE, Gram L, Johnsen AH et al. (2003). "Processing of seminal plasma hCAP-18 to ALL-38 by gastricsin – a novel mechanism of generating antimicrobial peptides in vagina.". J Biol Chem. 278 (31): 28540–6. doi:10.1074/jbc.M301608200. PMID 12759353. 
• De Yang , Chen Q, Schmidt AP, et al. (2000). "LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells.". J. Exp. Med. 192 (7): 1069–74. doi:10.1084/jem.192.7.1069. PMC 2193321. PMID 11015447. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2193321. 
• Agerberth B, Charo J, Werr J, et al. (2000). "The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations.". Blood 96 (9): 3086–93. PMID 11049988. 
• Bals R, Lang C, Weiner DJ, et al. (2001). "Rhesus monkey (Macaca mulatta) mucosal antimicrobial peptides are close homologues of human molecules.". Clin. Diagn. Lab. Immunol. 8 (2): 370–5. doi:10.1128/CDLI.8.2.370-375.2001. PMC 96065. PMID 11238224. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=96065. 
• Sørensen OE, Follin P, Johnsen AH, et al. (2001). "Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3.". Blood 97 (12): 3951–9. doi:10.1182/blood.V97.12.3951. PMID 11389039. 
• Nagaoka I, Hirota S, Niyonsaba F, et al. (2001). "Cathelicidin family of antibacterial peptides CAP18 and CAP11 inhibit the expression of TNF-alpha by blocking the binding of LPS to CD14(+) cells.". J. Immunol. 167 (6): 3329–38. PMID 11544322. 
• Hase K, Eckmann L, Leopard JD, et al. (2002). "Cell differentiation is a key determinant of cathelicidin LL-37/human cationic antimicrobial protein 18 expression by human colon epithelium.". Infect. Immun. 70 (2): 953–63. doi:10.1128/IAI.70.2.953-963.2002. PMC 127717. PMID 11796631. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=127717. 
• Giuliani A, Pirri G, Nicoletto S (2007). "Antimicrobial peptides: an overview of a promising class of therapeutics .". Cent. Eur. J. Biol. 2 (1): 1–33. doi:10.2478/s11535-007-0010-5. 
• Burton MF, Steel PG (2009). "Chemistry and Biology of LL-37". Natural Product Reports, 26 (12): 1572–1584. doi:10.1039/b912533g.