Family S60


Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq Architecture

Summary for family S60

Family type peptidaseS60.001 - lactoferrin (Homo sapiens), MEROPS Accession MER0020365 (peptidase unit: 20-357)
Content of familyFamily S60 contains a endopeptidase.
History Identifier created: MEROPS 6.3 (23 June 2003)
Lactoferrin is an iron glycoprotein that plays an important role in defence against pathogenic bacteria, fungi, protozoa and viruses. Most of its antibacterial activity is due to its ability to sequester iron, and its binding to the lipid A component of the bacterial lipopolysaccharide cell wall (Valenti et al., 2004). Recently, lactoferrin has also been shown to be a serine peptidase.
Catalytic typeSerine
Active site residuesK93 S279 
Active siteAn active site Lys/Ser dyad has been identified by site-directed mutagenesis Hendrixson et al., 2003.
Activities and specificitiesLactoferrin cleaves and inactivates two Haemophilus influenzae endopeptidases from peptidase family S6: the serine-type IgA endopeptidase (S06.007) and the hap peptidase (S06.006; Plaut et al., 2000). The EspB protein from Escherichia coli, a component of the type III secretion system and a key element in E. coli pathogenesis, is also cleaved (Ochoa & Clearly, 2004). Lactoferrin also undergoes autolytic cleavage and hydrolyses the synthetic substrate Z-Phe-Argaminomethylcoumarin (Massucci et al., 2004). Cleavage occurs at arginyl and lysyl bonds.
InhibitorsThe serine peptidase inhibitor phenylmethanesulfonyl fluoride (PMSF) has been shown to be inhibitory (Massucci et al., 2004).
Molecular structureThe tertiary structure of lactoferrin was first determined by Anderson et al. (1989). The structure contains two repeats, of which only the N-terminal bears active site residues. A structural ferric ion bridges both repeats. Each repeat forms a structural domain unlike that of any other peptidase.
Distribution of family Bacteria -  
Archaea details  
Protozoa -  
Fungi -  
Plants details  
Animals details  
Viruses -  
Biological functionsLactoferrin is synthesized by neutrophils and cells of exocrine glands in the form of a precursor with an N-terminal signal peptide. Peptides from lactoferrin have been reported to be peptidase inhibitors. Lactoferrin, and the internal peptide Tyr679-Lys695, have been shown to inhibit cathepsin L (C01.032; Ohashi et al., 2003), and lactoferrin has been shown to inhibit tryptase (S01.015; Ki 24 nM) probably by binding to heparin, which stabilizes the tryptase homotetramer (Elrod et al., 1997). Nothing is known of the biological significance of the peptidase activity.
Statistics for family S60Sequences:1127
Identifiers with PDB entries:5
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH
PFAM PF00405
SCOP 53888
Peptidases and Homologues MEROPS ID Structure
lactotransferrin precursor, domain 2S60.970Yes
serotransferrin precursor (domain 1)S60.972Yes
melanotransferrin domain 1S60.973-
Aa2-001 protein (Rattus norvegicus)S60.974-
serotransferrin precursor (domain 2)S60.975Yes
melanotransferrin domain 2S60.976-
1300017J02Rik proteinS60.977Yes
transferrin homologue proteinS60.978-
1300017J02Rik protein domain 2 (Mus musculus)S60.979-
Family S60 non-peptidase homologuesnon-peptidase homologue-
Family S60 unassigned peptidasesunassigned-