Cathelicidin

Cathelicidin antimicrobial peptide
Rendering based on PDB 2FBS.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2FBS, 2FBU, 2FCG, 2K6O, 2LMF, 4EYC
Identifiers
Symbols	CAMP ; CAP-18; CAP18; CRAMP; FALL-39; FALL39; HSD26; LL37
External IDs	OMIM: 600474 MGI: 108443 HomoloGene: 110678 GeneCards: CAMP Gene
Gene ontology Molecular function • protein binding Cellular component • extracellular space • cell wall • cytosol • extracellular exosome Biological process • innate immune response in mucosa • antibacterial humoral response • defense response to bacterium • negative regulation of growth of symbiont on or near host surface • defense response to Gram-positive bacterium • interaction with host • killing by host of symbiont cells • phagosome maturation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	820	12796
Ensembl	ENSG00000164047	ENSMUSG00000038357
UniProt	P49913	P51437
RefSeq (mRNA)	NM_004345	NM_009921
RefSeq (protein)	NP_004336	NP_034051
Location (UCSC)	Chr 3: 48.22 – 48.23 Mb	Chr 9: 109.85 – 109.85 Mb
PubMed search	[1]	[2]

Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs), and keratinocytes. Cathelicidins serve a critical role in mammalian innate immune defense against invasive bacterial infection. The cathelicidin family of peptides are classified as antimicrobial peptides (AMPs). The AMP family also includes the defensins. Whilst the defensins share common structural features, cathelicidin-related peptides are highly heterogeneous.

Members of the cathelicidin family of antimicrobial polypeptides are characterized by a highly conserved region (cathelin domain) and a highly variable cathelicidin peptide domain.

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.

Characteristics

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 superfamily	236
OPM protein	2k6o
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Cathelicidins range in size from 12 to 80 amino acid residues and have a wide range of structures. Most cathelicidins are linear peptides with 23-37 amino acid residues, and fold into amphiphatic α-helices. Additionally cathelicidins may also be small-sized molecules (12-18 residues) with beta-hairpin structures, stabilized by one or two disulphide bonds. Even larger cathelicidin peptides (39-80 amino acid residues) are also present. These larger cathelicidins display repetitive proline motifs forming extended polyproline-type structures.

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 family components have been found in: humans, monkeys, mice, rats, rabbits, guinea pigs, pandas, pigs, cattle, frogs, sheep, goats, chickens, and horses.

Currently identified cathelicidins include the following:

• Human:hCAP-18/LL-37
• Rhesus Monkey: RL-37
• Mice:CRAMP-1/2, (Cathelicidin-related Antimicrobial Peptide
• Rats: rCRAMP
• Rabbits: CAP-18
• Guinea Pig: CAP-11
• Pigs: PR-39, Prophenin, PMAP-23,36,37
• Cattle: BMAP-27,28,34 (Bovine Myeloid Antimicrobial Peptides); Bac5, Bac7
• Frogs: cathelicidin-AL (found in Amolops loloensis)
• Sheep:
• Goats:
• Chickens: Four cathelicidins, fowlicidins 1,2,3 and cathelicidin Beta-1
• Horses:
• Pandas:

Clinical significance

Patients with rosacea have elevated levels of cathelicidin and elevated levels of stratum corneum tryptic enzymes (SCTEs). Cathelicidin is cleaved into the antimicrobial peptide LL-37 by both kallikrein 5 and kallikrein 7 serine proteases. Excessive production of LL-37 is suspected to be a contributing cause in all subtypes of Rosacea. 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 up-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.

Vitamin D up-regulates genetic expression of cathelicidin, which exhibits broad-spectrum microbicidal activity against bacteria, fungi, and viruses. Cathelicidin rapidly destroys the lipoprotein membranes of microbes enveloped in phagosomes after fusion with lysosomes in macrophages.

See also

• Antimicrobial peptides
• Innate immune system
• Richard Gallo