Family S60

Family

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

Summary for family S60

Family type peptidase	S60.001 - lactoferrin (Homo sapiens), MEROPS Accession MER0020365 (peptidase unit: 20-357)
Content of family	Family 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 type	Serine
Active site residues	K93 S279
Active site	An active site Lys/Ser dyad has been identified by site-directed mutagenesis Hendrixson et al., 2003.
Activities and specificities	Lactoferrin 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.
Inhibitors	The serine peptidase inhibitor phenylmethanesulfonyl fluoride (PMSF) has been shown to be inhibitory (Massucci et al., 2004).
Molecular structure	The 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.
Clan	SR

Distribution of family	Bacteria	-
	Archaea	details
	Protozoa	-
	Fungi	-
	Plants	details
	Animals	details
	Viruses	-

Biological functions	Lactoferrin 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; K_i 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 S60	Sequences:	1127
	Identifiers:	11
	Identifiers with PDB entries:	5
Downloadable files	Sequence library (FastA format)
	Sequence alignment (FastA format)
	Phylogenetic tree (Newick format)

Other databases	CATH	3.40.190.10
	INTERPRO	IPR001156
	PANTHER	PTHR11485
	PFAM	PF00405
	SCOP	53888

Peptidases and Homologues	MEROPS ID	Structure
lactoferrin	S60.001	Yes
lactotransferrin precursor, domain 2	S60.970	Yes
hemiferrin	S60.971	-
serotransferrin precursor (domain 1)	S60.972	Yes
melanotransferrin domain 1	S60.973	-
Aa2-001 protein (Rattus norvegicus)	S60.974	-
serotransferrin precursor (domain 2)	S60.975	Yes
melanotransferrin domain 2	S60.976	-
1300017J02Rik protein	S60.977	Yes
transferrin homologue protein	S60.978	-
1300017J02Rik protein domain 2 (Mus musculus)	S60.979	-
Family S60 non-peptidase homologues	non-peptidase homologue	-
Family S60 unassigned peptidases	unassigned	-