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P02788 Proteins Transferrin-like domain Repeats
Uniprot ID:P02788
Protein name: Lactotransferrin
Gene : LTF GIG12 LF
Protein Family:Transferrin family
Squence Length : 710
Sequnce
>P02788 711 MKLVFLVLLFLGALGLCLAGRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAARRARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK
Domains
DOMAIN 25 352 Transferrin-like 1 DOMAIN 364 695 Transferrin-like 2
Transferrin-like sequence regions
25 - 352 WCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSE 364 - 695 WCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCS
Function
"Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate.; Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity, which depends on the extracellular cation concentration. 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. Can also prevent bacterial biofilm development in P.aeruginosa infection. Has weak antifungal activity against C.albicans. Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection. Can inhibit papillomavirus infections. 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. Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells. Stimulates VEGFA-mediated endothelial cell migration and proliferation. Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs). Also binds specifically to pneumococcal surface protein A (pspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA.; Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection. N-terminal region shows strong antifungal activity against C.albicans. Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site.; Kaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes.; Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors.; 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.; Isoform DeltaLf: transcription factor with antiproliferative properties and ability to induce cell cycle arrest. Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELENOH promoters"
Active Site
ACT_SITE 92 92 . ACT_SITE 278 278 Nucleophile
Binding Site
BINDING 23 23 PspA. BINDING 32 32 PspA. BINDING 136 136 Carbonate or oxalate 1. BINDING 140 140 Carbonate or oxalate 1. BINDING 142 142 Carbonate or oxalate 1. via amide nitrogen. BINDING 143 143 Carbonate or oxalate 1. via amide nitrogen. BINDING 480 480 Carbonate or oxalate 2. BINDING 484 484 Carbonate or oxalate 2. BINDING 486 486 Carbonate or oxalate 2. via amide nitrogen. BINDING 487 487 Carbonate or oxalate 2. via amide nitrogen
Mutation
"20 23 Missing: Abolishes binding to heparin, lipid A, lysozyme and DNA 20 22 Missing: Greatly impairs binding to heparin, lipid A, lysozyme and DNA 20 21 Missing: Impairs binding to heparin, lipid A, lysozyme and DNA 79 79 D->S: Impairs iron binding and changes domain closure 92 92 K->A: Almost no protease activity 140 140 R->D,E,S: Disrupts anion binding site and destabilizes iron binding 229 229 R->G,E: Destabilizes iron binding slightly 229 229 R->K,L: Destabilizes iron binding significantly 270 270 P->V: No effect 272 272 H->A,C,G,E,F,L,M,P,Q,T,Y: Destabilizes iron binding 278 278 S->A: No protease activity"