TRLF_DESRO
ID TRLF_DESRO Reviewed; 708 AA.
AC K9IMD0; M0QRM3;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 06-FEB-2013, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Lactotransferrin {ECO:0000305};
DE Short=Lactoferrin {ECO:0000305};
DE EC=3.4.21.- {ECO:0000250|UniProtKB:P02788};
DE AltName: Full=Draculin {ECO:0000303|PubMed:7740503};
DE AltName: Full=Draculin-1 {ECO:0000303|PubMed:23748026};
DE Flags: Precursor;
GN Name=LTF {ECO:0000250|UniProtKB:P02788};
OS Desmodus rotundus (Vampire bat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Chiroptera; Microchiroptera; Phyllostomidae;
OC Desmodontinae; Desmodus.
OX NCBI_TaxID=9430 {ECO:0000312|EMBL:JAA48810.1};
RN [1] {ECO:0000312|EMBL:JAA48810.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Salivary gland {ECO:0000312|EMBL:JAA48810.1};
RX PubMed=23411029; DOI=10.1016/j.jprot.2013.01.009;
RA Francischetti I.M., Assumpcao T.C., Ma D., Li Y., Vicente E.C., Uieda W.,
RA Ribeiro J.M.;
RT "The 'Vampirome': Transcriptome and proteome analysis of the principal and
RT accessory submaxillary glands of the vampire bat Desmodus rotundus, a
RT vector of human rabies.";
RL J. Proteomics 82:288-319(2013).
RN [2] {ECO:0000312|EMBL:JAA65087.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-388, IDENTIFICATION BY MASS SPECTROMETRY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23748026; DOI=10.1016/j.jprot.2013.05.034;
RA Low D.H., Sunagar K., Undheim E.A., Ali S.A., Alagon A.C., Ruder T.,
RA Jackson T.N., Pineda Gonzalez S., King G.F., Jones A., Antunes A.,
RA Fry B.G.;
RT "Dracula's children: molecular evolution of vampire bat venom.";
RL J. Proteomics 89:95-111(2013).
RN [3] {ECO:0000305}
RP PROTEIN SEQUENCE OF 20-32, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DISULFIDE BONDS.
RX PubMed=7740503;
RA Apitz-Castro R., Beguin S., Tablante A., Bartoli F., Holt J.C.,
RA Hemker H.C.;
RT "Purification and partial characterization of draculin, the anticoagulant
RT factor present in the saliva of vampire bats (Desmodus rotundus).";
RL Thromb. Haemost. 73:94-100(1995).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX PubMed=9795244; DOI=10.1016/s0304-4165(98)00082-8;
RA Fernandez A.Z., Tablante A., Bartoli F., Beguin S., Hemker H.C.,
RA Apitz-Castro R.;
RT "Expression of biological activity of draculin, the anticoagulant factor
RT from vampire bat saliva, is strictly dependent on the appropriate
RT glycosylation of the native molecule.";
RL Biochim. Biophys. Acta 1425:291-299(1998).
RN [5] {ECO:0000305}
RP FUNCTION, INTERACTION WITH COAGULATION FACTOR X, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=10556567; DOI=10.1016/s0167-4838(99)00160-0;
RA Fernandez A.Z., Tablante A., Beguin S., Hemker H.C., Apitz-Castro R.;
RT "Draculin, the anticoagulant factor in vampire bat saliva, is a tight-
RT binding, noncompetitive inhibitor of activated factor X.";
RL Biochim. Biophys. Acta 1434:135-142(1999).
CC -!- FUNCTION: Transferrins are iron binding transport proteins which can
CC bind two Fe(3+) ions in association with the binding of an anion,
CC usually bicarbonate. {ECO:0000250|UniProtKB:P02788}.
CC -!- FUNCTION: [Lactotransferrin]: Major iron-binding and multifunctional
CC protein found in exocrine fluids such as breast milk and mucosal
CC secretions. Has antimicrobial activity. Antimicrobial properties may
CC include bacteriostasis, which is related to its ability to sequester
CC free iron and thus inhibit microbial growth, as well as direct
CC bactericidal properties leading to the release of lipopolysaccharides
CC from the bacterial outer membrane. May have anabolic, differentiating
CC and anti-apoptotic effects on osteoblasts and may also inhibit
CC osteoclastogenesis, possibly playing a role in the regulation of bone
CC growth. May interfere with the lipopolysaccharide (LPS)-stimulated TLR4
CC signaling. {ECO:0000250|UniProtKB:P02788}.
CC -!- FUNCTION: The lactotransferrin transferrin-like domain 1 functions as a
CC serine protease of the peptidase S60 family that cuts arginine rich
CC regions. This function contributes to the antimicrobial activity. Shows
CC a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-,
CC and of Z-Phe-Arg-|-aminomethylcoumarin sites.
CC {ECO:0000250|UniProtKB:P02788}.
CC -!- FUNCTION: Acts as an anticoagulant of the blood coagulation cascade of
CC the bat's prey by inhibiting coagulation factor IX and activated
CC coagulation factor X. {ECO:0000269|PubMed:10556567,
CC ECO:0000269|PubMed:7740503, ECO:0000269|PubMed:9795244}.
CC -!- SUBUNIT: Monomer (PubMed:7740503). Found in a complex with LTF, CLU,
CC EPPIN and SEMG1 (By similarity). Interacts with prey activated
CC coagulation factor X; the interaction inhibits coagulation factor X
CC catalytic activity (PubMed:10556567). {ECO:0000250|UniProtKB:P02788,
CC ECO:0000269|PubMed:10556567, ECO:0000269|PubMed:7740503}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10556567,
CC ECO:0000269|PubMed:23748026, ECO:0000269|PubMed:7740503,
CC ECO:0000269|PubMed:9795244}.
CC -!- TISSUE SPECIFICITY: Expressed in the submaxillary gland and secreted in
CC the saliva (at protein level). {ECO:0000269|PubMed:10556567,
CC ECO:0000269|PubMed:23748026, ECO:0000269|PubMed:7740503,
CC ECO:0000269|PubMed:9795244}.
CC -!- PTM: N-glycosylated (PubMed:9795244). Glycosylation is important for
CC draculin anticoagulant activity (PubMed:9795244). Probably also O-
CC glycosylated (PubMed:9795244). {ECO:0000269|PubMed:9795244}.
CC -!- SIMILARITY: Belongs to the transferrin family.
CC {ECO:0000255|PIRNR:PIRNR002549}.
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DR EMBL; GABZ01004715; JAA48810.1; -; mRNA.
DR EMBL; GAEE01000036; JAA65087.1; -; mRNA.
DR AlphaFoldDB; K9IMD0; -.
DR SMR; K9IMD0; -.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0002376; P:immune system process; IEA:UniProtKB-KW.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:UniProtKB.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR InterPro; IPR016357; Transferrin.
DR InterPro; IPR001156; Transferrin-like_dom.
DR InterPro; IPR018195; Transferrin_Fe_BS.
DR Pfam; PF00405; Transferrin; 2.
DR PIRSF; PIRSF002549; Transferrin; 1.
DR PRINTS; PR00422; TRANSFERRIN.
DR SMART; SM00094; TR_FER; 2.
DR PROSITE; PS00206; TRANSFERRIN_LIKE_2; 1.
DR PROSITE; PS00207; TRANSFERRIN_LIKE_3; 2.
DR PROSITE; PS51408; TRANSFERRIN_LIKE_4; 2.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Blood coagulation cascade inhibiting toxin;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Immunity; Ion transport; Iron;
KW Iron transport; Metal-binding; Osteogenesis; Protease; Repeat; Secreted;
KW Serine protease; Signal; Toxin; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:7740503"
FT CHAIN 20..708
FT /note="Lactotransferrin"
FT /evidence="ECO:0000269|PubMed:7740503"
FT /id="PRO_5003930826"
FT DOMAIN 25..352
FT /note="Transferrin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DOMAIN 364..693
FT /note="Transferrin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT ACT_SITE 92
FT /evidence="ECO:0000250|UniProtKB:P02788"
FT ACT_SITE 278
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P02788"
FT BINDING 79
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 111
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 136
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 140
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 142
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 143
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 211
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 272
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 414
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 452
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 478
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 482
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 484
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 485
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 545
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 614
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 28..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 38..55
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 134..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 176..192
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 179..202
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 189..200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 250..264
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 367..399
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 377..390
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 476..551
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 510..524
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 521..534
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 592..606
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT CONFLICT 351..388
FT /note="KESAAEVEARGARVVWCAVGPEELRKCQQWSGQSNGTV -> NGIGSRGGDP
FT GGPGLCGARWAQRSCASASSGVARAMGQ (in Ref. 2; JAA65087)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 708 AA; 76856 MW; FCE2D59EB821A3D8 CRC64;
MKLLFLALLS LLALGPSLAA RRRGVRWCTI SKPEAAKCSK LQQNLKRVRG PSLSCISRKS
YLECIQAIAA KRADAMSLDA GLVYEAGQDP YRLRPVAAEV YGTEGAPRTH YYAVALVKKD
SNLQLNQLQG VRSCHTGLNR SAGWKIPVGT LRPYLGWAGP PAPLQEAVAN FFSASCVPCA
DGNQYPNLCR LCAGTGADKC ACSSKEPYFG YSGAFKCLKD GAGDVAFVKD STVFENLPNK
AERDQYELLC PDNTRKPVDE FEQCHLARVP SHAVVARSVG GKEDSIWRLL SKAQEKFGKG
TSGSFQLFSS PPGQKDLLFK DGAQGFLRIP SRVDAELYLG PSYLTVIKNL KESAAEVEAR
GARVVWCAVG PEELRKCQQW SGQSNGTVTC TTAADTEDCI ALVLKGEADA MSLDGGVIYI
AGKCGLAPVL AESQRSEGGS NLDCVNRPLE GDRAVAVVRK SSAGLTWNSR RGTKSCHTAV
GRTAGWNIPM GLLFNQTRSC NFDEFFSQSC APGADPNSNL CALCVGNEQG QDKCAPNSNE
RYFSYAGSFR CLVENAGDVA FVKASTVLEN PDGRGTEAWA KDLKLEDFEL LCLDGTRKPV
SEFETCHLAR APSHGVVSRK DRVQYLEQVL LDQQGKFGRN GPLCPGKFCL FQSETKNLLF
NDNTECLAKL QGKTTYEKYL GPEYVTAVAN LRQCSTSPLL EACTFLRN
