TRFL_PIG
ID TRFL_PIG Reviewed; 704 AA.
AC P14632; Q29557;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 3.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Lactotransferrin;
DE Short=Lactoferrin;
DE EC=3.4.21.-;
DE Flags: Precursor;
GN Name=LTF;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=1503259; DOI=10.1111/j.1365-2052.1992.tb00137.x;
RA Alexander L.J., Levine W.B., Teng C.T., Beattie C.W.;
RT "Cloning and sequencing of the porcine lactoferrin cDNA.";
RL Anim. Genet. 23:251-256(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=1511016; DOI=10.1016/0167-4781(92)90061-4;
RA Lyndon J.P., O'Malley B.R., Saucedo O., Lee T., Headon D.R., Conneely O.M.;
RT "Nucleotide and primary amino acid sequence of porcine lactoferrin.";
RL Biochim. Biophys. Acta 1132:97-99(1992).
RN [3]
RP PROTEIN SEQUENCE OF 20-49.
RX PubMed=2605266; DOI=10.1016/0167-4838(89)90015-0;
RA Hutchens T.W., Magnuson J.S., Yip T.-T.;
RT "Rapid purification of porcine colostral whey lactoferrin by affinity
RT chromatography on single-stranded DNA-agarose. Characterization, amino acid
RT composition and N-terminal amino acid sequence.";
RL Biochim. Biophys. Acta 999:323-329(1989).
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. 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 (By similarity). {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 (By
CC similarity). {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 -!- SIMILARITY: Belongs to the transferrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00741}.
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DR EMBL; M81327; AAA31059.1; -; mRNA.
DR EMBL; M92089; AAA31102.1; -; mRNA.
DR PIR; A45543; A45543.
DR RefSeq; NP_999527.1; NM_214362.1.
DR AlphaFoldDB; P14632; -.
DR SMR; P14632; -.
DR STRING; 9823.ENSSSCP00000026769; -.
DR MEROPS; S60.001; -.
DR MEROPS; S60.970; -.
DR PaxDb; P14632; -.
DR PeptideAtlas; P14632; -.
DR PRIDE; P14632; -.
DR GeneID; 397649; -.
DR KEGG; ssc:397649; -.
DR CTD; 4057; -.
DR eggNOG; ENOG502QSZB; Eukaryota.
DR InParanoid; P14632; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0042581; C:specific granule; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IEA:InterPro.
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:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR GO; GO:0006826; P:iron ion transport; IBA:GO_Central.
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; IPR030684; Lactotransferrin.
DR InterPro; IPR016357; Transferrin.
DR InterPro; IPR001156; Transferrin-like_dom.
DR InterPro; IPR018195; Transferrin_Fe_BS.
DR Pfam; PF00405; Transferrin; 2.
DR PIRSF; PIRSF500683; Lactotransferrin; 1.
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 Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Immunity; Ion transport; Iron; Iron transport; Metal-binding; Osteogenesis;
KW Protease; Reference proteome; Repeat; Secreted; Serine protease; Signal;
KW Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:2605266"
FT CHAIN 20..704
FT /note="Lactotransferrin"
FT /id="PRO_0000035738"
FT DOMAIN 25..348
FT /note="Transferrin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DOMAIN 360..689
FT /note="Transferrin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT ACT_SITE 88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT ACT_SITE 274
FT /note="Nucleophile"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 77
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 107
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 132
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
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 138
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 139
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 207
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 268
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 410
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 448
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 474
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
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 480
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 481
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 541
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT BINDING 610
FT /ligand="Fe(3+)"
FT /ligand_id="ChEBI:CHEBI:29034"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..62
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 38..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 130..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 172..188
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 185..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 246..260
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 363..395
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 373..386
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 420..699
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 472..547
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 496..690
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 506..520
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 517..530
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 588..602
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DISULFID 640..645
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT CONFLICT 12
FT /note="G -> W (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 46..48
FT /note="RRT -> TTR (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 51
FT /note="M -> I (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 85
FT /note="D -> G (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 121
FT /note="Missing (in Ref. 1; AAA31059)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="T -> I (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="E -> S (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="E -> Q (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 590
FT /note="D -> N (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="V -> M (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 662
FT /note="V -> C (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
FT CONFLICT 686..704
FT /note="NLKQCSVSPLLEACAFMMR -> T (in Ref. 2; AAA31102)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 77626 MW; 93261EFD608AD358 CRC64;
MKLFIPALLF LGTLGLCLAA PKKGVRWCVI STAEYSKCRQ WQSKIRRTNP MFCIRRASPT
DCIRAIAAKR ADAVTLDGGL VFEADQYKLR PVAAEIYGTE ENPQTYYYAV AVVKKGFNFQ
LNQLQGRKSC HTGLGRSAGW NIPIGLLRRF LDWAGPPEPL QKAVAKFFSQ SCVPCADGNA
YPNLCQLCIG KGKDKCACSS QEPYFGYSGA FNCLHKGIGD VAFVKESTVF ENLPQKADRD
KYELLCPDNT RKPVEAFREC HLARVPSHAV VARSVNGKEN SIWELLYQSQ KKFGKSNPQE
FQLFGSPGQQ KDLLFRDATI GFLKIPSKID SKLYLGLPYL TAIQGLRETA AEVEARQAKV
VWCAVGPEEL RKCRQWSSQS SQNLNCSLAS TTEDCIVQVL KGEADAMSLD GGFIYTAGKC
GLVPVLAENQ KSRQSSSSDC VHRPTQGYFA VAVVRKANGG ITWNSVRGTK SCHTAVDRTA
GWNIPMGLLV NQTGSCKFDE FFSQSCAPGS QPGSNLCALC VGNDQGVDKC VPNSNERYYG
YTGAFRCLAE NAGDVAFVKD VTVLDNTNGQ NTEEWARELR SDDFELLCLD GTRKPVTEAQ
NCHLAVAPSH AVVSRKEKAA QVEQVLLTEQ AQFGRYGKDC PDKFCLFRSE TKNLLFNDNT
EVLAQLQGKT TYEKYLGSEY VTAIANLKQC SVSPLLEACA FMMR
