| IED ID | IndEnz0002010428 |
| Enzyme Type ID | protease010428 |
| Protein Name |
Lactotransferrin Lactoferrin EC 3.4.21.- |
| Gene Name | LTF |
| Organism | Bubalus bubalis (Domestic water buffalo) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Artiodactyla Ruminantia Pecora Bovidae Bovinae Bubalus Bubalus bubalis (Domestic water buffalo) |
| Enzyme Sequence | MKLFVPALLSLGALGLCLAAPRKNVRWCTISQPEWLKCHRWQWRMKKLGAPSITCVRRAFVLECIRAITEKKADAVTLDGGMVFEAGLDPYKLRPVAAEIYGTKESPQTHYYAVAVVKKGSNFQLDQLQGRNSCHTGLGRSAGWNIPMGILRPYLSWTESLEPFQGAVAKFFSASCVPCVDRQAYPNLCQLCKGEGENQCACSPREPYFGYSGAFKCLQDGAGDVAFVKETTVFENLPEKADRDQYELLCLNNTRAPVDAFKECHLAQVPSHAVVARSVDGKEDLIWKLLSKAQEKFGKNKSGSFQLFGSPPGQRDLLFKDCALGFLRIPSKVDSALYLGSRYLTALKNLRETAEEVQARRARVVWCAVGPEEQKKCQQWSQQSGQIVTCATASTTDDCIALVLKGEADALSLDGGYIYTAGKCGLVPVLAENRKSSKHSSLDCVLRPTEGYLAVAVVKKANEGLTWNSLKGKKSCHTAVDRTAGWNIPMGLIANQTGSCAFDEFFSQSCAPGADPKSRLCALCAGDDQGLDKCVPNSKEKYYGYTGAFRCLAEDVGDVAFVKNDTVWENTNGESTADWAKNLNREDFRLLCLDGTRKPVTEAQSCHLAVAPNHAVVSLSERAAHVEQVLLHQQALFGENGKNCPDKFCLFKSETKNLLFNDNTECLAKLGGRPTYEEYLGTEYVTAIANLKKCSTSPLLEACAFLTR |
| Enzyme Length | 708 |
| Uniprot Accession Number | O77698 |
| Absorption | |
| Active Site | ACT_SITE 92; /evidence=ECO:0000255|PROSITE-ProRule:PRU00741; ACT_SITE 278; /note=Nucleophile; /evidence=ECO:0000255|PROSITE-ProRule:PRU00741 |
| Activity Regulation | |
| Binding Site | BINDING 136; /note="Carbonate 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 140; /note="Carbonate 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 142; /note="Carbonate 1; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 143; /note="Carbonate 1; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 478; /note="Carbonate 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 482; /note="Carbonate 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 484; /note="Carbonate 2; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; BINDING 485; /note="Carbonate 2; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344" |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.21.- |
| Enzyme Function | FUNCTION: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.; FUNCTION: Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity. Antimicrobial properties may include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane. The most effective inhibitory activity is seen against E.coli and P.aeruginosa. Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. Interferes with the lipopolysaccharide (LPS)-stimulated TLR4 signaling, but cannot directly stimulate the TLR4 signaling pathway and subsequent NF-kappa-B activation (By similarity). {ECO:0000250}.; FUNCTION: The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity. Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Beta strand (32); Binding site (8); Chain (1); Disulfide bond (17); Domain (2); Glycosylation (4); Helix (29); Metal binding (8); Signal peptide (1); Turn (14) |
| Keywords | 3D-structure;Disulfide bond;Glycoprotein;Hydrolase;Immunity;Ion transport;Iron;Iron transport;Metal-binding;Osteogenesis;Protease;Repeat;Secreted;Serine protease;Signal;Transport |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Secreted. Cytoplasmic granule {ECO:0000250}. Note=Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils (By similarity). {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | SIGNAL 1..19 |
| Structure 3D | X-ray crystallography (2) |
| Cross Reference PDB | 1BIY; 1CE2; |
| Mapped Pubmed ID | 1550358; 9398529; |
| Motif | |
| Gene Encoded By | |
| Mass | 77,730 |
| Kinetics | |
| Metal Binding | METAL 79; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 111; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 211; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 272; /note="Fe(3+) 1; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 414; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 452; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 545; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344"; METAL 614; /note="Fe(3+) 2; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10531476, ECO:0000269|PubMed:10818344" |
| Rhea ID | |
| Cross Reference Brenda |