IED Industry Enzyme Database

Detail Information for IndEnz0002001004
IED ID IndEnz0002001004
Enzyme Type ID protease001004
Protein Name Lactotransferrin
Lactoferrin
EC 3.4.21.-
Growth-inhibiting protein 12
Talalactoferrin

Cleaved into: Lactoferricin-H
Lfcin-H
; Kaliocin-1; Lactoferroxin-A; Lactoferroxin-B; Lactoferroxin-C
Gene Name LTF GIG12 LF
Organism Homo sapiens (Human)
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 Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human)
Enzyme Sequence MKLVFLVLLFLGALGLCLAGRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAARRARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK
Enzyme Length 710
Uniprot Accession Number P02788
Absorption
Active Site ACT_SITE 92; /evidence=ECO:0000305|PubMed:12535064; ACT_SITE 278; /note=Nucleophile; /evidence=ECO:0000305|PubMed:12535064
Activity Regulation
Binding Site BINDING 136; /note="Carbonate 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 140; /note="Carbonate 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 142; /note="Carbonate 1; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 143; /note="Carbonate 1; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 480; /note="Carbonate 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 484; /note="Carbonate 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 486; /note="Carbonate 2; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; BINDING 487; /note="Carbonate 2; via amide nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
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. {ECO:0000269|PubMed:22900286}.; FUNCTION: [Lactotransferrin]: Major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Has antimicrobial activity, which depends on the extracellular cation concentration (PubMed:6802759). Antimicrobial properties 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 (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987, PubMed:11179314, PubMed:12693969). Can also prevent bacterial biofilm development in P.aeruginosa infection (PubMed:12037568). Has weak antifungal activity against C.albicans (PubMed:11083624). Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth (PubMed:15166119). Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection (PubMed:17079302). Can inhibit papillomavirus infections (PubMed:17481742). Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with the lipopolysaccharide (LPS)-stimulated TLR4 signaling (PubMed:20345905). Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells (PubMed:19033648). Stimulates VEGFA-mediated endothelial cell migration and proliferation (PubMed:16842782). Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs) (PubMed:9359845). Also binds specifically to pneumococcal surface protein A (PspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA (PubMed:9359845). {ECO:0000269|PubMed:11083624, ECO:0000269|PubMed:11179314, ECO:0000269|PubMed:12037568, ECO:0000269|PubMed:12693969, ECO:0000269|PubMed:14573629, ECO:0000269|PubMed:15166119, ECO:0000269|PubMed:1599934, ECO:0000269|PubMed:16842782, ECO:0000269|PubMed:17079302, ECO:0000269|PubMed:17481742, ECO:0000269|PubMed:19033648, ECO:0000269|PubMed:20345905, ECO:0000269|PubMed:3169987, ECO:0000269|PubMed:6802759, ECO:0000269|PubMed:9359845}.; FUNCTION: Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection (PubMed:17481742). N-terminal region shows strong antifungal activity against C.albicans (PubMed:11083624). Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site. {ECO:0000269|PubMed:11083624, ECO:0000269|PubMed:17481742}.; FUNCTION: [Kaliocin-1]: Has antimicrobial activity and is able to permeabilize different ions through liposomal membranes. {ECO:0000269|PubMed:12693969}.; FUNCTION: [Lactoferroxin-A]: Has opioid antagonist activity (PubMed:1369293). Shows preference for mu-receptor (PubMed:1369293). {ECO:0000269|PubMed:1369293}.; FUNCTION: [Lactoferroxin-B]: Has opioid antagonist activity (PubMed:1369293). Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293). {ECO:0000269|PubMed:1369293}.; FUNCTION: [Lactoferroxin-C]: Has opioid antagonist activity (PubMed:1369293). Shows higher degrees of preference for kappa-receptors than for mu-receptors (PubMed:1369293). {ECO:0000269|PubMed:1369293}.; FUNCTION: The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions (PubMed:12535064). This function contributes to the antimicrobial activity (PubMed:12535064). Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites (PubMed:12535064). {ECO:0000269|PubMed:12535064}.; FUNCTION: [Isoform DeltaLf]: Transcription factor with antiproliferative properties and ability to induce cell cycle arrest (PubMed:15222485). Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters (PubMed:22320386). {ECO:0000269|PubMed:15222485, ECO:0000269|PubMed:22320386}.
Temperature Dependency
PH Dependency
Pathway
nucleotide Binding
Features Active site (2); Alternative sequence (1); Beta strand (36); Binding site (8); Chain (1); Cross-link (2); Disulfide bond (16); Domain (2); Glycosylation (4); Helix (36); Metal binding (8); Modified residue (1); Mutagenesis (11); Natural variant (6); Peptide (5); Region (8); Sequence conflict (19); Signal peptide (1); Site (3); Turn (11)
Keywords 3D-structure;Alternative promoter usage;Antibiotic;Antimicrobial;Cytoplasm;DNA-binding;Direct protein sequencing;Disulfide bond;Glycoprotein;Heparin-binding;Hydrolase;Immunity;Ion transport;Iron;Iron transport;Isopeptide bond;Metal-binding;Nucleus;Osteogenesis;Protease;Reference proteome;Repeat;Secreted;Serine protease;Signal;Transcription;Transcription regulation;Transport;Ubl conjugation
Interact With P62157; P75358; P75390; P75391; P75392; P78031; P27958; P27958
Induction
Subcellular Location SUBCELLULAR LOCATION: [Isoform 1]: Secreted. Cytoplasmic granule. Note=Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.; SUBCELLULAR LOCATION: [Isoform DeltaLf]: Cytoplasm. Nucleus. Note=Mainly localized in the cytoplasm.
Modified Residue MOD_RES P02788-2:10; /note=Phosphoserine; alternate; /evidence=ECO:0000269|PubMed:20404350
Post Translational Modification PTM: [Isoform DeltaLf]: Phosphorylation at Ser-10 activates the transcriptional activity (PubMed:20404350). Phosphorylation at Ser-10 also promotes proteasomal degradation (PubMed:20404350). Alternatively can undergo O-GlcNAcylation at Ser-10 (PubMed:20404350). {ECO:0000269|PubMed:20404350}.; PTM: [Isoform DeltaLf]: O-GlcNAcylation at Ser-10 inhibits DNA binding and negatively regulates the transcriptional activity (PubMed:20404350). Alternatively can undergo phosphorylation at Ser-10 (PubMed:20404350). {ECO:0000269|PubMed:20404350}.; PTM: Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.
Signal Peptide SIGNAL 1..19; /evidence=ECO:0000269|PubMed:14573629
Structure 3D NMR spectroscopy (7); X-ray crystallography (25)
Cross Reference PDB 1B0L; 1BKA; 1CB6; 1DSN; 1EH3; 1FCK; 1H43; 1H44; 1H45; 1HSE; 1L5T; 1LCF; 1LCT; 1LFG; 1LFH; 1LFI; 1LGB; 1N76; 1SQY; 1U62; 1VFD; 1VFE; 1XV4; 1XV7; 1Z6V; 1Z6W; 2BJJ; 2DP4; 2GMC; 2GMD; 2HD4; 2PMS;
Mapped Pubmed ID 10391242; 10411933; 10583407; 11313366; 11401442; 11467836; 11549422; 11697537; 11748357; 11756570; 11787671; 118839; 11908638; 11908641; 11911118; 11937551; 11981562; 12065686; 12097406; 12165435; 12165535; 12296849; 12438385; 12522210; 12525164; 12646274; 1270801; 12774664; 12788072; 12826902; 15221967; 15222484; 15229136; 15297857; 15364102; 15378004; 1544444; 15525592; 15543612; 15793153; 15955101; 15962837; 16152584; 16208406; 16261253; 16261256; 16432833; 16644090; 16650524; 16769765; 16787913; 16820307; 16936800; 16936805; 16954396; 17015741; 17030385; 17208010; 17211147; 17342646; 17353931; 17390038; 17461450; 17475866; 17476971; 17503830; 17515863; 17568188; 17597152; 17601350; 17703412; 17947640; 18022620; 18156281; 18285402; 1837051; 18449172; 18453607; 18484335; 1849145; 18619616; 18697201; 18785755; 18973542; 18977241; 19240970; 19258923; 19282435; 19334538; 19348738; 19382280; 19435495; 19454813; 19563039; 19651866; 19834535; 19916937; 19997820; 20136960; 20155438; 20207115; 20237496; 20238236; 20360068; 20401683; 20411301; 20452482; 20485928; 20503287; 20587610; 20594128; 20598696; 20668874; 20673868; 20711500; 20807650; 20922188; 20963400; 20972893; 21055448; 21163060; 2118650; 21400573; 21525168; 21572958; 21575138; 21935933; 21937479; 2195544; 22006997; 22011934; 22173721; 22226679; 22232695; 22261723; 22380846; 22433582; 22523385; 22553915; 22731992; 22763972; 22806010; 22810585; 23069661; 2330032; 23333090; 23386615; 23427237; 23460521; 23479198; 23602568; 23650620; 24077968; 2409350; 24217007; 24340941; 24442915; 24571258; 24831229; 24970346; 25057912; 25193851; 25236863; 25405719; 25535701; 25784250; 25914748; 25916224; 25946246; 25998152; 26279447; 26366224; 26405758; 26431065; 26445132; 26469086; 26649297; 26722419; 26874351; 26981846; 27017926; 27203426; 27234407; 27234408; 27234411; 27453322; 27497404; 27569531; 27685526; 27727130; 27902700; 27903408; 279930; 27997265; 28472424; 28485077; 28494220; 28652573; 28678770; 2900981; 29068673; 29165086; 29279524; 29453656; 29550924; 29809052; 29921139; 29989276; 30338705; 3035556; 3053705; 3080684; 3094007; 31048205; 31295370; 31396786; 3142462; 31443387; 31499027; 31582209; 31661123; 32352945; 32376620; 32586758; 32721184; 32811647; 32962819; 33486678; 33498631; 34353321; 34616691; 34659251; 3470756; 8097946; 8159701; 8464497; 8490014; 8870004; 9006323; 9054935; 9223490; 9862427;
Motif
Gene Encoded By
Mass 78,182
Kinetics
Metal Binding METAL 79; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 111; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 211; /note="Fe(3+) 1"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 272; /note="Fe(3+) 1; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 414; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 454; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 547; /note="Fe(3+) 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"; METAL 616; /note="Fe(3+) 2; via tele nitrogen"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00741, ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980, ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335, ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
Rhea ID
Cross Reference Brenda