TRFL_CAPHI
ID TRFL_CAPHI Reviewed; 708 AA.
AC Q29477; Q29479;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 110.
DE RecName: Full=Lactotransferrin;
DE Short=Lactoferrin;
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=LTF;
OS Capra hircus (Goat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Capra.
OX NCBI_TaxID=9925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=8093048; DOI=10.1006/bbrc.1994.2327;
RA le Provost F., Nocart M., Guerin G., Martin P.;
RT "Characterization of the goat lactoferrin cDNA. Assignment of the relevant
RT locus to bovine U12 synteny group.";
RL Biochem. Biophys. Res. Commun. 203:1324-1332(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], ANTIBACTERIAL ACTIVITY, AND DEVELOPMENTAL
RP STAGE.
RC STRAIN=Korean Native; TISSUE=Mammary gland;
RX PubMed=9363601; DOI=10.1111/j.1365-2052.1997.00154.x;
RA Lee T.H., Shimazaki K., Yu S.L., Nam M.S., Kim S.J., Lee K.K., Yu D.Y.;
RT "Polymorphic sequence of Korean Native goat lactoferrin exhibiting greater
RT antibacterial activity.";
RL Anim. Genet. 28:367-369(1997).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (4.00 ANGSTROMS) OF 20-708 IN COMPLEX WITH IRON.
RX PubMed=22896884;
RA Kumar P., Yadav S., Singh T.P.;
RT "Crystallization and structure determination of goat lactoferrin at 4.0A
RT resolution: A new form of packing in lactoferrins with a high solvent
RT content in crystals.";
RL Indian J. Biochem. Biophys. 39:16-21(2002).
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.
CC -!- FUNCTION: Lactotransferrin is a 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. The most effective inhibitory
CC activity is seen against E.coli and P.aeruginosa. Has anabolic,
CC differentiating and anti-apoptotic effects on osteoblasts and can also
CC inhibit osteoclastogenesis, possibly playing a role in the regulation
CC of bone growth. Interferes with the lipopolysaccharide (LPS)-stimulated
CC TLR4 signaling, but cannot directly stimulate the TLR4 signaling
CC pathway and subsequent NF-kappa-B activation (By similarity).
CC {ECO:0000250}.
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. {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted. Cytoplasmic granule {ECO:0000250}.
CC Note=Secreted into most exocrine fluids by various endothelial cells.
CC Stored in the secondary granules of neutrophils (By similarity).
CC {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Expressed in mammary glands at various stages of
CC development, with weak expression detected in virgin goats and during
CC pregnancy and lactation and high expression detected at the stage of
CC involution. {ECO:0000269|PubMed:9363601}.
CC -!- SIMILARITY: Belongs to the transferrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00741}.
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DR EMBL; X78902; CAA55517.1; -; mRNA.
DR EMBL; U53857; AAA97958.1; -; mRNA.
DR PIR; JC2323; JC2323.
DR RefSeq; NP_001272477.1; NM_001285548.1.
DR PDB; 1JW1; X-ray; 4.00 A; A=20-708.
DR PDBsum; 1JW1; -.
DR AlphaFoldDB; Q29477; -.
DR SMR; Q29477; -.
DR STRING; 9925.ENSCHIP00000016996; -.
DR MEROPS; S60.001; -.
DR PRIDE; Q29477; -.
DR GeneID; 100861194; -.
DR KEGG; chx:100861194; -.
DR CTD; 4057; -.
DR OrthoDB; 232859at2759; -.
DR EvolutionaryTrace; Q29477; -.
DR Proteomes; UP000291000; Unassembled WGS sequence.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0042581; C:specific granule; ISS: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:0019731; P:antibacterial humoral response; ISS:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; ISS:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; ISS:UniProtKB.
DR GO; GO:0006811; P:ion transport; IEA:UniProtKB-KW.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:2001205; P:negative regulation of osteoclast development; ISS:UniProtKB.
DR GO; GO:1900229; P:negative regulation of single-species biofilm formation in or on host organism; ISS:UniProtKB.
DR GO; GO:2000308; P:negative regulation of tumor necrosis factor (ligand) superfamily member 11 production; ISS:UniProtKB.
DR GO; GO:0001503; P:ossification; IEA:UniProtKB-KW.
DR GO; GO:1900159; P:positive regulation of bone mineralization involved in bone maturation; ISS:UniProtKB.
DR GO; GO:1902732; P:positive regulation of chondrocyte proliferation; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0001817; P:regulation of cytokine production; ISS:UniProtKB.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISS:UniProtKB.
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; PS00205; TRANSFERRIN_LIKE_1; 2.
DR PROSITE; PS00206; TRANSFERRIN_LIKE_2; 2.
DR PROSITE; PS00207; TRANSFERRIN_LIKE_3; 2.
DR PROSITE; PS51408; TRANSFERRIN_LIKE_4; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Immunity;
KW Ion transport; Iron; Iron transport; Metal-binding; Osteogenesis; Protease;
KW Reference proteome; Repeat; Secreted; Serine protease; Signal; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000250"
FT CHAIN 20..708
FT /note="Lactotransferrin"
FT /id="PRO_0000035730"
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:0000255|PROSITE-ProRule:PRU00741"
FT ACT_SITE 278
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
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 ECO:0000269|PubMed:22896884"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..64
FT DISULFID 38..55
FT DISULFID 134..217
FT DISULFID 176..192
FT DISULFID 179..202
FT DISULFID 189..200
FT DISULFID 250..264
FT DISULFID 367..399
FT DISULFID 377..390
FT DISULFID 424..703
FT DISULFID 444..666
FT DISULFID 476..551
FT DISULFID 500..694
FT DISULFID 510..524
FT DISULFID 521..534
FT DISULFID 592..606
FT DISULFID 644..649
FT CONFLICT 56
FT /note="I -> V (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="L -> R (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
FT CONFLICT 124
FT /note="Q -> K (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="F -> P (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="S -> R (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="D -> G (in Ref. 1; CAA55517)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 708 AA; 77358 MW; F2EDA3C83539960D CRC64;
MKLFVPALLS LGALGLCLAA PRKNVRWCAI SLPEWSKCYQ WQRRMRKLGA PSITCIRRTS
ALECIRAIAG KNADAVTLDS GMVFEAGLDP YKLRPVAAEI YGTEKSPQTH YYAVAVVKKG
SNFQLDQLQG QKSCHMGLGR SAGWNIPVGI LRPFLSWTES AEPLQGAVAR FFSASCVPCV
DGKAYPNLCQ LCKGVGENKC ACSSQEPYFG YSGAFKCLQD GAGDVAFVKE TTVFENLPEK
ADRDQYELLC LNNTRAPVDA FKECHLAQVP SHAVVARSVD GKENLIWELL RKAQEKFGKN
KSQSFQLFGS PEGRRDLLFK DSALGFVRIP SKVDSALYLG SRYLTALKNL RETAEELKAR
CTRVVWCAVG PEEQSKCQQW SEQSGQNVTC ATASTTDDCI ALVLKGEADA LSLDGGYIYT
AGKCGLVPVM AENRKSSKYS SLDCVLRPTE GYLAVAVVKK ANEGLTWNSL KGKKSCHTAV
DRTAGWNIPM GLIANQTGSC AFDEFFSQSC APGADPKSSL CALCAGDDQG LDKCVPNSKE
KYYGYTGAFR CLAEDVGDVA FVKNDTVWEN TNGESSADWA KNLNREDFRL LCLDGTTKPV
TEAQSCYLAV APNHAVVSRS DRAAHVEQVL LHQQALFGKN GKNCPDQFCL FKSETKNLLF
NDNTECLAKL GGRPTYEKYL GTEYVTAIAN LKKCSTSPLL EACAFLTR
