TRFL_HUMAN
ID TRFL_HUMAN Reviewed; 710 AA.
AC P02788; A8K9U8; B2MV13; B7Z4X2; E7EQH5; O00756; Q16780; Q16785; Q16786;
AC Q16789; Q5DSM0; Q8IU92; Q8IZH6; Q8TCD2; Q96KZ4; Q96KZ5; Q9H1Z3; Q9UCY5;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 6.
DT 03-AUG-2022, entry version 251.
DE RecName: Full=Lactotransferrin;
DE Short=Lactoferrin;
DE EC=3.4.21.- {ECO:0000269|PubMed:12535064};
DE AltName: Full=Growth-inhibiting protein 12;
DE AltName: Full=Talalactoferrin;
DE Contains:
DE RecName: Full=Lactoferricin-H;
DE Short=Lfcin-H;
DE Contains:
DE RecName: Full=Kaliocin-1;
DE Contains:
DE RecName: Full=Lactoferroxin-A;
DE Contains:
DE RecName: Full=Lactoferroxin-B;
DE Contains:
DE RecName: Full=Lactoferroxin-C;
DE Flags: Precursor;
GN Name=LTF; Synonyms=GIG12, LF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-22 INS; THR-148
RP AND CYS-422.
RC TISSUE=Mammary gland;
RX PubMed=2402455; DOI=10.1093/nar/18.17.5288;
RA Rey M.W., Woloshuk S.L., de Boer H.A., Pieper F.R.;
RT "Complete nucleotide sequence of human mammary gland lactoferrin.";
RL Nucleic Acids Res. 18:5288-5288(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ARG-22 INS.
RC TISSUE=Mammary gland;
RA Cho Y.Y.;
RT "Cloning of human lactoferrin gene and its polymorphism in normal and
RT cancer cells.";
RL Thesis (1994), Genetic Engineering Research Institute, South Korea.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND DELTALF), ALTERNATIVE SPLICING,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=9122171; DOI=10.1073/pnas.94.6.2198;
RA Siebert P.D., Huang B.C.;
RT "Identification of an alternative form of human lactoferrin mRNA that is
RT expressed differentially in normal tissues and tumor-derived cell lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2198-2203(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-22 INS; THR-29;
RP ARG-47 AND ASP-579.
RC TISSUE=Mammary gland;
RX PubMed=11702692;
RA Cheng H., Chen X.Z., Huan L.D.;
RT "cDNA cloning and sequence analysis of human lactoferrin.";
RL Sheng Wu Gong Cheng Xue Bao 17:385-387(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), X-RAY CRYSTALLOGRAPHY (3.40
RP ANGSTROMS) OF 22-710 IN COMPLEX WITH IRON AND CARBONATE, FUNCTION, AND
RP VARIANTS ARG-22 INS; THR-29; ARG-47 AND ASP-579.
RC TISSUE=Seminal vesicle;
RX PubMed=22900286;
RA Kumar J., Weber W., Munchau S., Yadav S., Singh S.B., Saravanan K.,
RA Paramasivam M., Sharma S., Kaur P., Bhushan A., Srinivasan A., Betzel C.,
RA Singh T.P.;
RT "Crystal structure of human seminal diferric lactoferrin at 3.4 Angstrom
RT resolution.";
RL Indian J. Biochem. Biophys. 40:14-21(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 20-30,
RP FUNCTION, AND VARIANTS ARG-22 INS; THR-29 AND ARG-47.
RC TISSUE=Blood;
RX PubMed=14573629; DOI=10.1128/iai.71.11.6141-6147.2003;
RA Velliyagounder K., Kaplan J.B., Furgang D., Legarda D., Diamond G.,
RA Parkin R.E., Fine D.H.;
RT "One of two human lactoferrin variants exhibits increased antibacterial and
RT transcriptional activation activities and is associated with localized
RT juvenile periodontitis.";
RL Infect. Immun. 71:6141-6147(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Bone marrow;
RA Wei X., Han J., Rado T.A.;
RT "Human neutrophil lactoferrin coding and 5' flanking region DNA
RT sequences.";
RL Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-22 INS; THR-29 AND
RP ARG-47.
RC TISSUE=Prostate;
RA Conneely O.M.;
RL Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-22 INS; THR-29;
RP ARG-47 AND ASP-579.
RC TISSUE=Mammary gland;
RA Shi Y.-Q., Zhang Y., Zheng Y.-M.;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-22 INS AND
RP CYS-422.
RA Kim J.W.;
RT "Identification of a growth inhibition gene.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-22 INS; THR-29 AND
RP ARG-47.
RA Allayous C., Marianne-Pepin T.;
RT "Mutations in ELA2 and LTF genes.";
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND DELTALF), AND
RP VARIANT ARG-22 INS.
RC TISSUE=Lung, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-22 INS.
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
RX PubMed=1480183; DOI=10.1210/mend.6.11.1480183;
RA Teng C.T., Liu Y., Yang N., Walmer D., Panella T.;
RT "Differential molecular mechanism of the estrogen action that regulates
RT lactoferrin gene in human and mouse.";
RL Mol. Endocrinol. 6:1969-1981(1992).
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-710 (ISOFORM 1), AND VARIANT ARG-22 INS.
RC TISSUE=Mammary gland;
RX PubMed=2374734; DOI=10.1093/nar/18.13.4013;
RA Powell M.J., Ogden J.E.;
RT "Nucleotide sequence of human lactoferrin cDNA.";
RL Nucleic Acids Res. 18:4013-4013(1990).
RN [17]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-710 (ISOFORM 1), AND VARIANT ARG-22 INS.
RC TISSUE=Mammary gland;
RA Liang Q., Jimenez-Flores R., Richardson T.;
RT "Molecular cloning and sequence analysis of human lactoferrin.";
RL Submitted (DEC-1991) to the EMBL/GenBank/DDBJ databases.
RN [18]
RP PROTEIN SEQUENCE OF 20-710 (ISOFORM 1), AND DISULFIDE BONDS.
RX PubMed=6510420; DOI=10.1111/j.1432-1033.1984.tb08607.x;
RA Metz-Boutigue M.-H., Jolles J., Mazurier J., Schoentgen F., Legrand D.,
RA Spik G., Montreuil J., Jolles P.;
RT "Human lactotransferrin: amino acid sequence and structural comparisons
RT with other transferrins.";
RL Eur. J. Biochem. 145:659-676(1984).
RN [19]
RP PRELIMINARY PROTEIN SEQUENCE OF 20-72; 133-170; 256-277; 359-528 AND
RP 608-663 (ISOFORM 1).
RX PubMed=6794640; DOI=10.1016/0005-2795(81)90016-7;
RA Metz-Boutigue M.-H., Mazurier J., Jolles J., Spik G., Montreuil J.,
RA Jolles P.;
RT "The present state of the human lactotransferrin sequence. Study and
RT alignment of the cyanogen bromide fragments and characterization of N- and
RT C-terminal domains.";
RL Biochim. Biophys. Acta 670:243-254(1981).
RN [20]
RP PROTEIN SEQUENCE OF 20-65 (ISOFORM 1), IDENTIFICATION OF LACTOFERRICIN
RP PEPTIDE, FUNCTION, AND SYNTHESIS OF 36-58.
RC TISSUE=Milk;
RX PubMed=1599934; DOI=10.1016/0167-4838(92)90346-f;
RA Bellamy W., Takase M., Yamauchi K., Wakabayashi H., Kawase K., Tomita M.;
RT "Identification of the bactericidal domain of lactoferrin.";
RL Biochim. Biophys. Acta 1121:130-136(1992).
RN [21]
RP PROTEIN SEQUENCE OF 20-40 (ISOFORM 1), FUNCTION, GLYCOSAMINOGLYCAN BINDING,
RP AND SYNTHESIS OF 20-51; 20-45 AND 25-51.
RC TISSUE=Milk;
RX PubMed=8089135; DOI=10.1016/s0021-9258(17)31566-1;
RA Mann D.M., Romm E., Migliorini M.;
RT "Delineation of the glycosaminoglycan-binding site in the human
RT inflammatory response protein lactoferrin.";
RL J. Biol. Chem. 269:23661-23667(1994).
RN [22]
RP PROTEIN SEQUENCE OF 20-56 (ISOFORM 1).
RC TISSUE=Seminal plasma;
RX PubMed=8551695;
RA Sato I.;
RT "Characterization of the 84-kDa protein with ABH activity in human seminal
RT plasma.";
RL Nihon Hoigaku Zasshi 49:281-293(1995).
RN [23]
RP PROTEIN SEQUENCE OF 24-32; 38-43; 50-57 AND 59-67 (ISOFORM 1), STRUCTURE BY
RP NMR OF 20-67 (LACTOFERRICIN), MASS SPECTROMETRY, AND DISULFIDE BONDS.
RC TISSUE=Milk;
RX PubMed=16048952; DOI=10.1128/aac.49.8.3387-3395.2005;
RA Hunter H.N., Demcoe A.R., Jenssen H., Gutteberg T.J., Vogel H.J.;
RT "Human lactoferricin is partially folded in aqueous solution and is better
RT stabilized in a membrane mimetic solvent.";
RL Antimicrob. Agents Chemother. 49:3387-3395(2005).
RN [24]
RP PROTEIN SEQUENCE OF 38-57; 235-261; 509-525 AND 651-710, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Tear;
RX PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA Suarez T., Elortza F.;
RT "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT by in silico and in vitro analyses for antimicrobial peptide
RT identification.";
RL J. Proteome Res. 14:2649-2658(2015).
RN [25]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 236-710, AND VARIANT ASP-579.
RA McCombie W.R., Wilson R., Chen E., Gibbs R., Zuo L., Johnson D., Nhan M.,
RA Parnell L., Dedhia N., Ansari A., Mardis E., Schutz K., Gnoj L.,
RA la Bastide M., Kaplan N., Greco T., Touchman J., Muzny D., Chen C.N.,
RA Evans C., Fitzgerald M., See L.H., Tang M., Porcel B.M., Dragan Y.,
RA Giacalone J., Pae A., Powell E., Solinsky K.A., Desilva U., Diaz-Perez S.,
RA Zhou X., Yu Y., Watanabe M., Doggett N., Garcia D., Sagripanti J.L.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [26]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 435-710.
RC TISSUE=Myeloid;
RX PubMed=3477300;
RA Rado T.A., Wei X., Benz E.J. Jr.;
RT "Isolation of lactoferrin cDNA from a human myeloid library and expression
RT of mRNA during normal and leukemic myelopoiesis.";
RL Blood 70:989-993(1987).
RN [27]
RP PROTEIN SEQUENCE OF 608-710.
RX PubMed=7049727; DOI=10.1016/0014-5793(82)80229-9;
RA Metz-Boutigue M.-H., Jolles J., Mazurier J., Spik G., Montreuil J.,
RA Jolles P.;
RT "An 88 amino acid long C-terminal sequence of human lactotransferrin.";
RL FEBS Lett. 142:107-110(1982).
RN [28]
RP FUNCTION.
RX PubMed=6802759; DOI=10.1128/iai.35.3.792-799.1982;
RA Arnold R.R., Russell J.E., Champion W.J., Brewer M., Gauthier J.J.;
RT "Bactericidal activity of human lactoferrin: differentiation from the
RT stasis of iron deprivation.";
RL Infect. Immun. 35:792-799(1982).
RN [29]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=2981589;
RA Cramer E., Pryzwansky K.B., Villeval J.L., Testa U., Breton-Gorius J.;
RT "Ultrastructural localization of lactoferrin and myeloperoxidase in human
RT neutrophils by immunogold.";
RL Blood 65:423-432(1985).
RN [30]
RP FUNCTION.
RX PubMed=3169987; DOI=10.1128/iai.56.11.2774-2781.1988;
RA Ellison R.T. III, Giehl T.J., LaForce F.M.;
RT "Damage of the outer membrane of enteric gram-negative bacteria by
RT lactoferrin and transferrin.";
RL Infect. Immun. 56:2774-2781(1988).
RN [31]
RP CHARACTERIZATION OF LACTOFERROXINS.
RX PubMed=1369293; DOI=10.1271/bbb1961.54.1803;
RA Tani F., Iio K., Chiba H., Yoshikawa M.;
RT "Isolation and characterization of opioid antagonist peptides derived from
RT human lactoferrin.";
RL Agric. Biol. Chem. 54:1803-1810(1990).
RN [32]
RP FUNCTION, AND MUTAGENESIS OF 20-G--R-23.
RX PubMed=9359845; DOI=10.1042/bj3280145;
RA van Berkel P.H., Geerts M.E., van Veen H.A., Mericskay M., de Boer H.A.,
RA Nuijens J.H.;
RT "N-terminal stretch Arg2, Arg3, Arg4 and Arg5 of human lactoferrin is
RT essential for binding to heparin, bacterial lipopolysaccharide, human
RT lysozyme and DNA.";
RL Biochem. J. 328:145-151(1997).
RN [33]
RP FUNCTION.
RX PubMed=11083624; DOI=10.1128/aac.44.12.3257-3263.2000;
RA Lupetti A., Paulusma-Annema A., Welling M.M., Senesi S., van Dissel J.T.,
RA Nibbering P.H.;
RT "Candidacidal activities of human lactoferrin peptides derived from the N
RT terminus.";
RL Antimicrob. Agents Chemother. 44:3257-3263(2000).
RN [34]
RP TISSUE SPECIFICITY.
RX PubMed=10792619; DOI=10.1046/j.1523-1755.2000.00050.x;
RA Abrink M., Larsson E., Gobl A., Hellman L.;
RT "Expression of lactoferrin in the kidney: implications for innate immunity
RT and iron metabolism.";
RL Kidney Int. 57:2004-2010(2000).
RN [35]
RP FUNCTION, SYNTHESIS OF 20-29 AND 39-49, AND MUTAGENESIS OF 20-GLY--ARG-22.
RX PubMed=11179314; DOI=10.1128/iai.69.3.1469-1476.2001;
RA Nibbering P.H., Ravensbergen E., Welling M.M., van Berkel L.A.,
RA van Berkel P.H., Pauwels E.K., Nuijens J.H.;
RT "Human lactoferrin and peptides derived from its N terminus are highly
RT effective against infections with antibiotic-resistant bacteria.";
RL Infect. Immun. 69:1469-1476(2001).
RN [36]
RP FUNCTION.
RX PubMed=12037568; DOI=10.1038/417552a;
RA Singh P.K., Parsek M.R., Greenberg E.P., Welsh M.J.;
RT "A component of innate immunity prevents bacterial biofilm development.";
RL Nature 417:552-555(2002).
RN [37]
RP SUBCELLULAR LOCATION, AND ALTERNATIVE PROMOTER USAGE.
RX PubMed=12565886; DOI=10.1016/s0006-291x(02)03077-2;
RA Liu D., Wang X., Zhang Z., Teng C.T.;
RT "An intronic alternative promoter of the human lactoferrin gene is
RT activated by Ets.";
RL Biochem. Biophys. Res. Commun. 301:472-479(2003).
RN [38]
RP FUNCTION, AND SYNTHESIS OF 36-58 AND 171-201 (KALIOCIN-1).
RX PubMed=12693969; DOI=10.1023/a:1022657630698;
RA Viejo-Diaz M., Andres M.T., Perez-Gil J., Sanchez M., Fierro J.F.;
RT "Potassium efflux induced by a new lactoferrin-derived peptide mimicking
RT the effect of native human lactoferrin on the bacterial cytoplasmic
RT membrane.";
RL Biochemistry (Mosc.) 68:217-227(2003).
RN [39]
RP FUNCTION AS A PROTEASE, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF
RP LYS-92; PRO-270 AND SER-278.
RX PubMed=12535064; DOI=10.1046/j.1365-2958.2003.03327.x;
RA Hendrixson D.R., Qiu J., Shewry S.C., Fink D.L., Petty S., Baker E.N.,
RA Plaut A.G., St Geme J.W. III;
RT "Human milk lactoferrin is a serine protease that cleaves Haemophilus
RT surface proteins at arginine-rich sites.";
RL Mol. Microbiol. 47:607-617(2003).
RN [40]
RP FUNCTION, AND SUBCELLULAR LOCATION (DELTALF).
RX PubMed=15222485; DOI=10.1023/b:biom.0000027712.81056.13;
RA Breton M., Mariller C., Benaissa M., Caillaux K., Browaeys E., Masson M.,
RA Vilain J.P., Mazurier J., Pierce A.;
RT "Expression of delta-lactoferrin induces cell cycle arrest.";
RL BioMetals 17:325-329(2004).
RN [41]
RP FUNCTION.
RX PubMed=15166119; DOI=10.1210/en.2003-1307;
RA Cornish J., Callon K.E., Naot D., Palmano K.P., Banovic T., Bava U.,
RA Watson M., Lin J.M., Tong P.C., Chen Q., Chan V.A., Reid H.E.,
RA Fazzalari N., Baker H.M., Baker E.N., Haggarty N.W., Grey A.B., Reid I.R.;
RT "Lactoferrin is a potent regulator of bone cell activity and increases bone
RT formation in vivo.";
RL Endocrinology 145:4366-4374(2004).
RN [42]
RP FUNCTION.
RX PubMed=16842782; DOI=10.1016/j.febslet.2006.06.091;
RA Kim C.W., Son K.N., Choi S.Y., Kim J.;
RT "Human lactoferrin upregulates expression of KDR/Flk-1 and stimulates VEGF-
RT A-mediated endothelial cell proliferation and migration.";
RL FEBS Lett. 580:4332-4336(2006).
RN [43]
RP FUNCTION.
RX PubMed=17481742; DOI=10.1016/j.antiviral.2007.03.012;
RA Mistry N., Drobni P., Naslund J., Sunkari V.G., Jenssen H., Evander M.;
RT "The anti-papillomavirus activity of human and bovine lactoferricin.";
RL Antiviral Res. 75:258-265(2007).
RN [44]
RP IDENTIFICATION IN A COMPLEX WITH CLU; SEMG1 AND EPPIN.
RX PubMed=17567961; DOI=10.1095/biolreprod.107.060194;
RA Wang Z., Widgren E.E., Richardson R.T., O'Rand M.G.;
RT "Characterization of an eppin protein complex from human semen and
RT spermatozoa.";
RL Biol. Reprod. 77:476-484(2007).
RN [45]
RP FUNCTION.
RX PubMed=17079302; DOI=10.1128/jvi.01995-06;
RA Johansson C., Jonsson M., Marttila M., Persson D., Fan X.L., Skog J.,
RA Frangsmyr L., Wadell G., Arnberg N.;
RT "Adenoviruses use lactoferrin as a bridge for CAR-independent binding to
RT and infection of epithelial cells.";
RL J. Virol. 81:954-963(2007).
RN [46]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156; ASN-497 AND ASN-642.
RC TISSUE=Milk;
RX PubMed=18780401; DOI=10.1002/pmic.200701057;
RA Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
RT "Identification of N-linked glycoproteins in human milk by hydrophilic
RT interaction liquid chromatography and mass spectrometry.";
RL Proteomics 8:3833-3847(2008).
RN [47]
RP FUNCTION.
RX PubMed=19033648; DOI=10.1172/jci36226;
RA Bournazou I., Pound J.D., Duffin R., Bournazos S., Melville L.A.,
RA Brown S.B., Rossi A.G., Gregory C.D.;
RT "Apoptotic human cells inhibit migration of granulocytes via release of
RT lactoferrin.";
RL J. Clin. Invest. 119:20-32(2009).
RN [48]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-497.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [49]
RP FUNCTION, AND PTM.
RX PubMed=20345905; DOI=10.1111/j.1742-4658.2010.07620.x;
RA Ando K., Hasegawa K., Shindo K., Furusawa T., Fujino T., Kikugawa K.,
RA Nakano H., Takeuchi O., Akira S., Akiyama T., Gohda J., Inoue J.,
RA Hayakawa M.;
RT "Human lactoferrin activates NF-kappaB through the Toll-like receptor 4
RT pathway while it interferes with the lipopolysaccharide-stimulated TLR4
RT signaling.";
RL FEBS J. 277:2051-2066(2010).
RN [50]
RP GLYCOSYLATION AT SER-10 (ISOFORM DELTALF), PHOSPHORYLATION AT SER-10
RP (ISOFORM DELTALF), AND UBIQUITINATION AT LYS-379 AND LYS-391 (ISOFORM
RP DELTALF).
RX PubMed=20404350; DOI=10.1074/jbc.m109.080572;
RA Hardiville S., Hoedt E., Mariller C., Benaissa M., Pierce A.;
RT "O-GlcNAcylation/phosphorylation cycling at Ser10 controls both
RT transcriptional activity and stability of delta-lactoferrin.";
RL J. Biol. Chem. 285:19205-19218(2010).
RN [51]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [52]
RP FUNCTION AS A TRANSCRIPTION FACTOR (ISOFORM DELTALF), AND DNA-BINDING
RP (ISOFORM DELTALF).
RX PubMed=22320386; DOI=10.1139/o11-070;
RA Mariller C., Hardiville S., Hoedt E., Huvent I., Pina-Canseco S.,
RA Pierce A.;
RT "Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a
RT transcription factor.";
RL Biochem. Cell Biol. 90:307-319(2012).
RN [53]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [54]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), AND SEQUENCE REVISION.
RX PubMed=2585506; DOI=10.1016/0022-2836(89)90602-5;
RA Anderson B.F., Baker H.M., Norris G.E., Rice D.W., Baker E.N.;
RT "Structure of human lactoferrin: crystallographic structure analysis and
RT refinement at 2.8-A resolution.";
RL J. Mol. Biol. 209:711-734(1989).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 20-710.
RX PubMed=1772635; DOI=10.1107/s0108768191008418;
RA Norris G.E., Anderson B.F., Baker E.N.;
RT "Molecular replacement solution of the structure of apolactoferrin, a
RT protein displaying large-scale conformational change.";
RL Acta Crystallogr. B 47:998-1004(1991).
RN [56]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 20-710 IN COMPLEX WITH COPPER AND
RP CARBONATE, AND GLYCOSYLATION AT ASN-156 AND ASN-497.
RX PubMed=1581307; DOI=10.1021/bi00133a020;
RA Smith C.A., Anderson B.F., Baker H.M., Baker E.N.;
RT "Metal substitution in transferrins: the crystal structure of human copper-
RT lactoferrin at 2.1-A resolution.";
RL Biochemistry 31:4527-4533(1992).
RN [57]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 21-352 IN COMPLEX WITH IRON AND
RP CARBONATE, AND DISULFIDE BONDS.
RX PubMed=8371268; DOI=10.1006/jmbi.1993.1462;
RA Day C.L., Anderson B.F., Tweedie J.W., Baker E.N.;
RT "Structure of the recombinant N-terminal lobe of human lactoferrin at 2.0 A
RT resolution.";
RL J. Mol. Biol. 232:1084-1100(1993).
RN [58]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 20-710 IN COMPLEX WITH COPPER AND
RP OXALATE, AND GLYCOSYLATION AT ASN-156.
RX PubMed=15299444; DOI=10.1107/s0907444994000491;
RA Smith C.A., Anderson B.F., Baker H.M., Baker E.N.;
RT "Structure of copper- and oxalate-substituted human lactoferrin at 2.0 A
RT resolution.";
RL Acta Crystallogr. D 50:302-316(1994).
RN [59]
RP X-RAY CRYSTALLOGRAPHY (3.30 ANGSTROMS) OF 110-268, AND GLYCOSYLATION AT
RP ASN-156.
RX PubMed=8069634; DOI=10.1016/s0969-2126(00)00022-8;
RA Bourne Y., Mazurier J., Legrand D., Rouge P., Montreuil J., Spik G.,
RA Cambillau C.;
RT "Structures of a legume lectin complexed with the human lactotransferrin N2
RT fragment, and with an isolated biantennary glycopeptide: role of the fucose
RT moiety.";
RL Structure 2:209-219(1994).
RN [60]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-710 IN COMPLEX WITH IRON AND
RP CARBONATE, AND GLYCOSYLATION AT ASN-156 AND ASN-497.
RX PubMed=15299793; DOI=10.1107/s0907444994013521;
RA Haridas M., Anderson B.F., Baker E.N.;
RT "Structure of human diferric lactoferrin refined at 2.2-A resolution.";
RL Acta Crystallogr. D 51:629-646(1995).
RN [61]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 20-710 IN COMPLEX WITH IRON AND
RP OXALATE.
RX PubMed=8703903; DOI=10.1021/bi960288y;
RA Baker H.M., Anderson B.F., Brodie A.M., Shongwe M.S., Smith C.A.,
RA Baker E.N.;
RT "Anion binding by transferrins: importance of second-shell effects revealed
RT by the crystal structure of oxalate-substituted diferric lactoferrin.";
RL Biochemistry 35:9007-9013(1996).
RN [62]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 22-352 OF MUTANTS GLU-140 AND
RP SER-140 IN COMPLEX WITH IRON AND CARBONATE, AND MUTAGENESIS OF ARG-140.
RX PubMed=8931543; DOI=10.1021/bi961729g;
RA Faber H.R., Baker C.J., Day C.L., Tweedie J.W., Baker E.N.;
RT "Mutation of arginine 121 in lactoferrin destabilizes iron binding by
RT disruption of anion binding: crystal structures of R121S and R121E
RT mutants.";
RL Biochemistry 35:14473-14479(1996).
RN [63]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 21-352 OF MUTANT SER-79 IN
RP COMPLEX WITH IRON AND CARBONATE, AND MUTAGENESIS OF ASP-79.
RX PubMed=8594202; DOI=10.1006/jmbi.1996.0091;
RA Faber H.R., Bland T., Day C.L., Norris G.E., Tweedie J.W., Baker E.N.;
RT "Altered domain closure and iron binding in transferrins: the crystal
RT structure of the Asp60Ser mutant of the amino-terminal half-molecule of
RT human lactoferrin.";
RL J. Mol. Biol. 256:352-363(1996).
RN [64]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-353 OF MUTANT MET-272 IN
RP COMPLEX WITH IRON AND CARBONATE, AND MUTAGENESIS OF HIS-272.
RX PubMed=9003186; DOI=10.1021/bi961908y;
RA Nicholson H., Anderson B.F., Bland T., Shewry S.C., Tweedie J.W.,
RA Baker E.N.;
RT "Mutagenesis of the histidine ligand in human lactoferrin: iron binding
RT properties and crystal structure of the histidine-253-->methionine
RT mutant.";
RL Biochemistry 36:341-346(1997).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 20-710.
RX PubMed=10089508; DOI=10.1107/s0907444998004417;
RA Jameson G.B., Anderson B.F., Norris G.E., Thomas D.H., Baker E.N.;
RT "Structure of human apolactoferrin at 2.0 A resolution. Refinement and
RT analysis of ligand-induced conformational change.";
RL Acta Crystallogr. D 54:1319-1335(1998).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) 20-710 IN COMPLEX WITH IRON AND
RP CARBONATE.
RX PubMed=10089347; DOI=10.1107/s0907444998011226;
RA Sun X.L., Baker H.M., Shewry S.C., Jameson G.B., Baker E.N.;
RT "Structure of recombinant human lactoferrin expressed in Aspergillus
RT awamori.";
RL Acta Crystallogr. D 55:403-407(1999).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 21-348 OF MUTANT LYS-229 IN
RP COMPLEX WITH IRON AND CARBONATE, AND MUTAGENESIS OF ARG-229.
RX PubMed=10828980; DOI=10.1021/bi0001224;
RA Peterson N.A., Anderson B.F., Jameson G.B., Tweedie J.W., Baker E.N.;
RT "Crystal structure and iron-binding properties of the R210K mutant of the
RT N-lobe of human lactoferrin: implications for iron release from
RT transferrins.";
RL Biochemistry 39:6625-6633(2000).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 21-710 IN COMPLEX WITH CERIUM AND
RP CARBONATE.
RX PubMed=11128996; DOI=10.1007/s007750000157;
RA Baker H.M., Baker C.J., Smith C.A., Baker E.N.;
RT "Metal substitution in transferrins: specific binding of cerium(IV)
RT revealed by the crystal structure of cerium-substituted human
RT lactoferrin.";
RL J. Biol. Inorg. Chem. 5:692-698(2000).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 21-351 OF MUTANT ASP-140, AND
RP MUTAGENESIS OF ARG-140.
RX PubMed=12037297; DOI=10.1107/s0907444902005127;
RA Jameson G.B., Anderson B.F., Breyer W.A., Day C.L., Tweedie J.W.,
RA Baker E.N.;
RT "Structure of a domain-opened mutant (R121D) of the human lactoferrin N-
RT lobe refined from a merohedrally twinned crystal form.";
RL Acta Crystallogr. D 58:955-962(2002).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 21-352 OF MUTANTS GLY-229;
RP GLU-229 AND LEU-229 IN COMPLEX WITH IRON AND CARBONATE, AND MUTAGENESIS OF
RP ARG-229.
RX PubMed=12450380; DOI=10.1021/bi020443a;
RA Peterson N.A., Arcus V.L., Anderson B.F., Tweedie J.W., Jameson G.B.,
RA Baker E.N.;
RT "'Dilysine trigger' in transferrins probed by mutagenesis of lactoferrin:
RT crystal structures of the R210G, R210E, and R210L mutants of human
RT lactoferrin.";
RL Biochemistry 41:14167-14175(2002).
RN [71]
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 20-710 IN COMPLEX WITH IRON AND
RP CARBONATE, AND GLYCOSYLATION AT ASN-156 AND ASN-497.
RA Vikram P., Prem Kumar R., Singh N., Kumar J., Ethayathulla A.S., Sharma S.,
RA Kaur P., Singh T.P.;
RT "Structure of human diferric lactoferrin at 2.5A resolution using crystals
RT grown at pH 6.5.";
RL Submitted (MAR-2004) to the PDB data bank.
RN [72]
RP STRUCTURE BY NMR OF 39-49 IN COMPLEX WITH LIPOPOLYSACCHARIDE, AND SYNTHESIS
RP OF 39-49.
RX PubMed=15687491; DOI=10.1074/jbc.m500266200;
RA Japelj B., Pristovsek P., Majerle A., Jerala R.;
RT "Structural origin of endotoxin neutralization and antimicrobial activity
RT of a lactoferrin-based peptide.";
RL J. Biol. Chem. 280:16955-16961(2005).
RN [73]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 20-710 IN COMPLEX WITH IRON AND
RP CARBONATE, GLYCOSYLATION AT ASN-156 AND ASN-497, AND VARIANT ASP-579.
RX PubMed=16201406; DOI=10.1007/s11248-005-3233-0;
RA Thomassen E.A., van Veen H.A., van Berkel P.H., Nuijens J.H.,
RA Abrahams J.P.;
RT "The protein structure of recombinant human lactoferrin produced in the
RT milk of transgenic cows closely matches the structure of human milk-derived
RT lactoferrin.";
RL Transgenic Res. 14:397-405(2005).
RN [74]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 528-535 IN COMPLEX WITH
RP PROTEINASE K.
RA Singh A.K., Singh N., Sharma S., Bhushan A., Singh T.P.;
RT "Crystal structure of the complex formed between proteinase K and a human
RT lactoferrin fragment at 2.9 A resolution.";
RL Submitted (MAY-2006) to the PDB data bank.
RN [75]
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 528-535 IN COMPLEX WITH
RP PROTEINASE K.
RA Prem Kumar R., Singh A.K., Singh N., Kaur P., Sharma S., Singh T.P.;
RT "Crystal structure of proteinase K inhibited by a lactoferrin octapeptide
RT Gly-Asp-Glu-Gln-Gly-Glu-Asn-Lys at 2.15 A resolution.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [76]
RP STRUCTURE BY NMR OF 39-49.
RX PubMed=17263370; DOI=10.1021/ja067419v;
RA Japelj B., Zorko M., Majerle A., Pristovsek P., Sanchez-Gomez S.,
RA Martinez de Tejada G., Moriyon I., Blondelle S.E., Brandenburg K.,
RA Andra J., Lohner K., Jerala R.;
RT "The acyl group as the central element of the structural organization of
RT antimicrobial lipopeptide.";
RL J. Am. Chem. Soc. 129:1022-1023(2007).
RN [77]
RP X-RAY CRYSTALLOGRAPHY (2.91 ANGSTROMS) OF 21-362 IN COMPLEX WITH
RP PNEUMOCOCCAL SURFACE PROTEIN A FRAGMENT; IRON AND CARBONATE.
RX PubMed=17543335; DOI=10.1016/j.jmb.2007.04.075;
RA Senkovich O., Cook W.J., Mirza S., Hollingshead S.K., Protasevich I.I.,
RA Briles D.E., Chattopadhyay D.;
RT "Structure of a complex of human lactoferrin N-lobe with pneumococcal
RT surface protein a provides insight into microbial defense mechanism.";
RL J. Mol. Biol. 370:701-713(2007).
RN [78]
RP VARIANTS THR-29 AND ARG-47.
RX PubMed=9873069;
RA Klintworth G.K., Sommer J.R., Obrian G., Han L., Ahmed M.N., Qumsiyeh M.B.,
RA Lin P.-Y., Basti S., Reddy M.K., Kanai A., Hotta Y., Sugar J.,
RA Kumaramanickavel G., Munier F., Schorderet D.F., El Matri L., Iwata F.,
RA Kaiser-Kupfer M., Nagata M., Nakayasu K., Hejtmancik J.F., Teng C.T.;
RT "Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal
RT dystrophy): exclusion of linkage to lactoferrin gene.";
RL Mol. Vis. 4:31-32(1998).
RN [79]
RP VARIANTS ARG-22 INS AND ARG-47.
RX PubMed=22406253; DOI=10.1016/j.humimm.2012.02.014;
RA Videm V., Dahl H., Walberg L.E., Wiseth R.;
RT "Functional polymorphisms in the LTF gene and risk of coronary artery
RT stenosis.";
RL Hum. Immunol. 73:554-559(2012).
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:0000269|PubMed:22900286}.
CC -!- FUNCTION: [Lactotransferrin]: Major iron-binding and multifunctional
CC protein found in exocrine fluids such as breast milk and mucosal
CC secretions (PubMed:14573629, PubMed:1599934, PubMed:6802759,
CC PubMed:3169987, PubMed:11179314, PubMed:12693969). Has antimicrobial
CC activity, which depends on the extracellular cation concentration
CC (PubMed:6802759). Antimicrobial properties include bacteriostasis,
CC which is related to its ability to sequester free iron and thus inhibit
CC microbial growth, as well as direct bactericidal properties leading to
CC the release of lipopolysaccharides from the bacterial outer membrane
CC (PubMed:14573629, PubMed:1599934, PubMed:6802759, PubMed:3169987,
CC PubMed:11179314, PubMed:12693969). Can also prevent bacterial biofilm
CC development in P.aeruginosa infection (PubMed:12037568). Has weak
CC antifungal activity against C.albicans (PubMed:11083624). 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 (PubMed:15166119). Promotes binding of species C
CC adenoviruses to epithelial cells, promoting adenovirus infection
CC (PubMed:17079302). Can inhibit papillomavirus infections
CC (PubMed:17481742). Stimulates the TLR4 signaling pathway leading to NF-
CC kappa-B activation and subsequent pro-inflammatory cytokine production
CC while also interfering with the lipopolysaccharide (LPS)-stimulated
CC TLR4 signaling (PubMed:20345905). Inhibits neutrophil granulocyte
CC migration to sites of apoptosis, when secreted by apoptotic cells
CC (PubMed:19033648). Stimulates VEGFA-mediated endothelial cell migration
CC and proliferation (PubMed:16842782). Binds heparin, chondroitin sulfate
CC and possibly other glycosaminoglycans (GAGs) (PubMed:9359845). Also
CC binds specifically to pneumococcal surface protein A (PspA), the lipid
CC A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA
CC (PubMed:9359845). {ECO:0000269|PubMed:11083624,
CC ECO:0000269|PubMed:11179314, ECO:0000269|PubMed:12037568,
CC ECO:0000269|PubMed:12693969, ECO:0000269|PubMed:14573629,
CC ECO:0000269|PubMed:15166119, ECO:0000269|PubMed:1599934,
CC ECO:0000269|PubMed:16842782, ECO:0000269|PubMed:17079302,
CC ECO:0000269|PubMed:17481742, ECO:0000269|PubMed:19033648,
CC ECO:0000269|PubMed:20345905, ECO:0000269|PubMed:3169987,
CC ECO:0000269|PubMed:6802759, ECO:0000269|PubMed:9359845}.
CC -!- FUNCTION: Lactoferricin binds to the bacterial surface and is crucial
CC for the bactericidal functions. Has some antiviral activity against
CC papillomavirus infection (PubMed:17481742). N-terminal region shows
CC strong antifungal activity against C.albicans (PubMed:11083624).
CC Contains two BBXB heparin-binding consensus sequences that appear to
CC form the predominate functional GAG-binding site.
CC {ECO:0000269|PubMed:11083624, ECO:0000269|PubMed:17481742}.
CC -!- FUNCTION: [Kaliocin-1]: Has antimicrobial activity and is able to
CC permeabilize different ions through liposomal membranes.
CC {ECO:0000269|PubMed:12693969}.
CC -!- FUNCTION: [Lactoferroxin-A]: Has opioid antagonist activity
CC (PubMed:1369293). Shows preference for mu-receptor (PubMed:1369293).
CC {ECO:0000269|PubMed:1369293}.
CC -!- FUNCTION: [Lactoferroxin-B]: Has opioid antagonist activity
CC (PubMed:1369293). Shows higher degrees of preference for kappa-
CC receptors than for mu-receptors (PubMed:1369293).
CC {ECO:0000269|PubMed:1369293}.
CC -!- FUNCTION: [Lactoferroxin-C]: Has opioid antagonist activity
CC (PubMed:1369293). Shows higher degrees of preference for kappa-
CC receptors than for mu-receptors (PubMed:1369293).
CC {ECO:0000269|PubMed:1369293}.
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 (PubMed:12535064). This function contributes to the
CC antimicrobial activity (PubMed:12535064). Shows a preferential cleavage
CC at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-
CC aminomethylcoumarin sites (PubMed:12535064).
CC {ECO:0000269|PubMed:12535064}.
CC -!- FUNCTION: [Isoform DeltaLf]: Transcription factor with
CC antiproliferative properties and ability to induce cell cycle arrest
CC (PubMed:15222485). Binds to the DeltaLf response element found in the
CC SKP1, BAX, DCPS, and SELENOH promoters (PubMed:22320386).
CC {ECO:0000269|PubMed:15222485, ECO:0000269|PubMed:22320386}.
CC -!- SUBUNIT: Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1.
CC {ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
CC ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
CC ECO:0000269|PubMed:15299444, ECO:0000269|PubMed:15299793,
CC ECO:0000269|PubMed:15687491, ECO:0000269|PubMed:1581307,
CC ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
CC ECO:0000269|PubMed:17567961, ECO:0000269|PubMed:22900286,
CC ECO:0000269|PubMed:8371268, ECO:0000269|PubMed:8594202,
CC ECO:0000269|PubMed:8703903, ECO:0000269|PubMed:8931543,
CC ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71, ECO:0000269|Ref.74,
CC ECO:0000269|Ref.75}.
CC -!- INTERACTION:
CC P02788; P62157: CALM; Xeno; NbExp=2; IntAct=EBI-1058602, EBI-397403;
CC P02788; P75358: gapA; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-2259469;
CC P02788; P75390: pdhA; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-2259629;
CC P02788; P75391: pdhB; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-2259621;
CC P02788; P75392: pdhC; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-2259593;
CC P02788; P78031: pyk; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-2259473;
CC P02788; PRO_0000037569 [P27958]; Xeno; NbExp=3; IntAct=EBI-1058602, EBI-6904259;
CC P02788; PRO_0000037570 [P27958]; Xeno; NbExp=9; IntAct=EBI-1058602, EBI-6904269;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Secreted. Cytoplasmic granule.
CC Note=Secreted into most exocrine fluids by various endothelial cells.
CC Stored in the secondary granules of neutrophils.
CC -!- SUBCELLULAR LOCATION: [Isoform DeltaLf]: Cytoplasm. Nucleus.
CC Note=Mainly localized in the cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage; Named isoforms=2;
CC Name=1;
CC IsoId=P02788-1; Sequence=Displayed;
CC Name=DeltaLf; Synonyms=Delta-lactoferrin;
CC IsoId=P02788-2; Sequence=VSP_044308;
CC -!- TISSUE SPECIFICITY: High levels are found in saliva and tears,
CC intermediate levels in serum and plasma, and low levels in urine. In
CC kidney, detected in the distal collecting tubules in the medulla but
CC not in the cortical region or in blood vessels. Detected in peripheral
CC blood neutrophils (at protein level). Isoform 1 and isoform DeltaLf are
CC expressed in breast, prostate, spleen, pancreas, kidney, small
CC intestine, lung, skeletal muscle, uterus, thymus and fetal liver.
CC Isoform 1 is expressed in brain, testis and peripheral blood
CC leukocytes; isoform DeltaLf is barely detectable in these tissues.
CC Isoform DeltaLf is expressed in placenta, liver and ovary; isoform 1 is
CC barely detectable in these tissues. In kidney, isoform 1 is expressed
CC at high levels in the collecting tubules of the medulla but at very low
CC levels in the cortex. {ECO:0000269|PubMed:10792619,
CC ECO:0000269|PubMed:2981589, ECO:0000269|PubMed:9122171}.
CC -!- PTM: [Isoform DeltaLf]: Phosphorylation at Ser-10 activates the
CC transcriptional activity (PubMed:20404350). Phosphorylation at Ser-10
CC also promotes proteasomal degradation (PubMed:20404350). Alternatively
CC can undergo O-GlcNAcylation at Ser-10 (PubMed:20404350).
CC {ECO:0000269|PubMed:20404350}.
CC -!- PTM: [Isoform DeltaLf]: O-GlcNAcylation at Ser-10 inhibits DNA binding
CC and negatively regulates the transcriptional activity
CC (PubMed:20404350). Alternatively can undergo phosphorylation at Ser-10
CC (PubMed:20404350). {ECO:0000269|PubMed:20404350}.
CC -!- PTM: Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed
CC for TLR4 activation.
CC -!- MASS SPECTROMETRY: [Lactoferricin-H]: Mass=5737.8; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:16048952};
CC -!- POLYMORPHISM: The sequence shown corresponds to the reference genome
CC sequence and is likely to represent the minor allele, whereas most
CC publications refer to the longer sequence containing variant Arg-22
CC ins. Insertion of the additional arginine in variant Arg-22 ins creates
CC an N-terminal basic cluster of four arginines, all of which appear to
CC be important for the full functionality of the protein, including
CC bactericidal and antifungal activities as well as binding to
CC glycosaminoglycans, pspA, LPS, lysozyme and DNA.
CC -!- MISCELLANEOUS: [Isoform DeltaLf]: Contains a phosphoserine at position
CC 10 (alternate). Contains a O-linked (GlcNAc) serine at position 10
CC (alternate). O-GlcNAcylation at Ser-10 inhibits DNA binding and
CC negatively regulates DeltaLf transcriptional activity, whereas
CC phosphorylation activates it. Phosphorylation at Ser-10 also promotes
CC proteasomal degradation. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the transferrin family. {ECO:0000255|PROSITE-
CC ProRule:PRU00741}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Lactotransferrin entry;
CC URL="https://en.wikipedia.org/wiki/Lactotransferrin";
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DR EMBL; X53961; CAA37914.1; -; mRNA.
DR EMBL; U07643; AAB60324.1; -; mRNA.
DR EMBL; AF332168; AAG48753.1; -; mRNA.
DR EMBL; AY178998; AAN75578.2; -; mRNA.
DR EMBL; AY137470; AAN11304.1; -; mRNA.
DR EMBL; M73700; AAA59479.1; -; Genomic_DNA.
DR EMBL; M93150; AAA36159.1; -; mRNA.
DR EMBL; AY165046; AAN63998.1; -; mRNA.
DR EMBL; AY493417; AAS72878.1; -; mRNA.
DR EMBL; EU622050; ACC95966.1; -; Genomic_DNA.
DR EMBL; AK292813; BAF85502.1; -; mRNA.
DR EMBL; AK298035; BAH12708.1; -; mRNA.
DR EMBL; AC098613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015822; AAH15822.1; -; mRNA.
DR EMBL; BC015823; AAH15823.1; -; mRNA.
DR EMBL; BC022347; AAH22347.1; -; mRNA.
DR EMBL; S52659; AAB24877.1; -; Genomic_DNA.
DR EMBL; X52941; CAA37116.1; -; mRNA.
DR EMBL; M83202; AAA59511.1; -; mRNA.
DR EMBL; M83205; AAA58656.1; -; mRNA.
DR EMBL; U95626; AAB57795.1; -; Genomic_DNA.
DR EMBL; M18642; AAA86665.1; -; mRNA.
DR CCDS; CCDS33747.1; -. [P02788-1]
DR CCDS; CCDS56251.1; -. [P02788-2]
DR PIR; G01394; TFHUL.
DR RefSeq; NP_001186078.1; NM_001199149.1. [P02788-2]
DR RefSeq; NP_001308050.1; NM_001321121.1.
DR RefSeq; NP_001308051.1; NM_001321122.1.
DR RefSeq; NP_002334.2; NM_002343.5. [P02788-1]
DR PDB; 1B0L; X-ray; 2.20 A; A=20-710.
DR PDB; 1BKA; X-ray; 2.40 A; A=20-710.
DR PDB; 1CB6; X-ray; 2.00 A; A=20-710.
DR PDB; 1DSN; X-ray; 2.05 A; A=21-352.
DR PDB; 1EH3; X-ray; 2.00 A; A=21-352.
DR PDB; 1FCK; X-ray; 2.20 A; A=21-710.
DR PDB; 1H43; X-ray; 2.20 A; A=21-352.
DR PDB; 1H44; X-ray; 2.00 A; A=21-352.
DR PDB; 1H45; X-ray; 1.95 A; A=21-352.
DR PDB; 1HSE; X-ray; 2.20 A; A=21-353.
DR PDB; 1L5T; X-ray; 3.00 A; A/B=21-351.
DR PDB; 1LCF; X-ray; 2.00 A; A=20-710.
DR PDB; 1LCT; X-ray; 2.00 A; A=21-352.
DR PDB; 1LFG; X-ray; 2.20 A; A=20-710.
DR PDB; 1LFH; X-ray; 2.80 A; A=20-710.
DR PDB; 1LFI; X-ray; 2.10 A; A=20-710.
DR PDB; 1LGB; X-ray; 3.30 A; C=110-268.
DR PDB; 1N76; X-ray; 3.40 A; A=21-710.
DR PDB; 1SQY; X-ray; 2.50 A; A=20-710.
DR PDB; 1U62; NMR; -; A=39-49.
DR PDB; 1VFD; X-ray; 2.50 A; A=20-349.
DR PDB; 1VFE; X-ray; 2.30 A; A=20-352.
DR PDB; 1XV4; NMR; -; A=39-49.
DR PDB; 1XV7; NMR; -; A=39-49.
DR PDB; 1Z6V; NMR; -; A=21-67.
DR PDB; 1Z6W; NMR; -; A=21-67.
DR PDB; 2BJJ; X-ray; 2.40 A; X=21-710.
DR PDB; 2DP4; X-ray; 2.90 A; I=528-535.
DR PDB; 2GMC; NMR; -; A=39-49.
DR PDB; 2GMD; NMR; -; A=39-49.
DR PDB; 2HD4; X-ray; 2.15 A; B=528-535.
DR PDB; 2PMS; X-ray; 2.91 A; A/B=21-362.
DR PDB; 7N88; EM; 3.70 A; B=20-710.
DR PDBsum; 1B0L; -.
DR PDBsum; 1BKA; -.
DR PDBsum; 1CB6; -.
DR PDBsum; 1DSN; -.
DR PDBsum; 1EH3; -.
DR PDBsum; 1FCK; -.
DR PDBsum; 1H43; -.
DR PDBsum; 1H44; -.
DR PDBsum; 1H45; -.
DR PDBsum; 1HSE; -.
DR PDBsum; 1L5T; -.
DR PDBsum; 1LCF; -.
DR PDBsum; 1LCT; -.
DR PDBsum; 1LFG; -.
DR PDBsum; 1LFH; -.
DR PDBsum; 1LFI; -.
DR PDBsum; 1LGB; -.
DR PDBsum; 1N76; -.
DR PDBsum; 1SQY; -.
DR PDBsum; 1U62; -.
DR PDBsum; 1VFD; -.
DR PDBsum; 1VFE; -.
DR PDBsum; 1XV4; -.
DR PDBsum; 1XV7; -.
DR PDBsum; 1Z6V; -.
DR PDBsum; 1Z6W; -.
DR PDBsum; 2BJJ; -.
DR PDBsum; 2DP4; -.
DR PDBsum; 2GMC; -.
DR PDBsum; 2GMD; -.
DR PDBsum; 2HD4; -.
DR PDBsum; 2PMS; -.
DR PDBsum; 7N88; -.
DR AlphaFoldDB; P02788; -.
DR SASBDB; P02788; -.
DR SMR; P02788; -.
DR BioGRID; 110235; 143.
DR CORUM; P02788; -.
DR DIP; DIP-41354N; -.
DR IntAct; P02788; 51.
DR MINT; P02788; -.
DR STRING; 9606.ENSP00000231751; -.
DR ChEMBL; CHEMBL4523161; -.
DR DrugBank; DB06987; (R)-Atenolol.
DR DrugBank; DB01811; 3h-Indole-5,6-Diol.
DR DrugBank; DB03485; alpha-D-Fucopyranose.
DR DrugBank; DB06784; Gallium citrate Ga-67.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB04743; Nimesulide.
DR DrugBank; DB03040; Nitrilotriacetic acid.
DR DrugBank; DB08439; Parecoxib.
DR DrugBank; DB11182; Rose bengal.
DR Allergome; 1384; Hom s LF.
DR MEROPS; S60.001; -.
DR MEROPS; S60.970; -.
DR GlyConnect; 2842; 5 N-Linked glycans.
DR GlyConnect; 320; 168 N-Linked glycans (3 sites), 2 O-Linked glycans (1 site).
DR GlyGen; P02788; 6 sites, 145 N-linked glycans (4 sites), 3 O-linked glycans (2 sites).
DR iPTMnet; P02788; -.
DR PhosphoSitePlus; P02788; -.
DR BioMuta; LTF; -.
DR DMDM; 85700158; -.
DR EPD; P02788; -.
DR jPOST; P02788; -.
DR MassIVE; P02788; -.
DR PaxDb; P02788; -.
DR PeptideAtlas; P02788; -.
DR PRIDE; P02788; -.
DR ProteomicsDB; 51597; -. [P02788-1]
DR ProteomicsDB; 6642; -.
DR Antibodypedia; 3271; 1371 antibodies from 44 providers.
DR DNASU; 4057; -.
DR Ensembl; ENST00000231751.9; ENSP00000231751.4; ENSG00000012223.13. [P02788-1]
DR Ensembl; ENST00000426532.6; ENSP00000405719.2; ENSG00000012223.13. [P02788-2]
DR GeneID; 4057; -.
DR KEGG; hsa:4057; -.
DR MANE-Select; ENST00000231751.9; ENSP00000231751.4; NM_002343.6; NP_002334.2.
DR UCSC; uc003fzr.4; human. [P02788-1]
DR CTD; 4057; -.
DR DisGeNET; 4057; -.
DR GeneCards; LTF; -.
DR HGNC; HGNC:6720; LTF.
DR HPA; ENSG00000012223; Group enriched (bone marrow, salivary gland).
DR MIM; 150210; gene.
DR neXtProt; NX_P02788; -.
DR OpenTargets; ENSG00000012223; -.
DR PharmGKB; PA30482; -.
DR VEuPathDB; HostDB:ENSG00000012223; -.
DR eggNOG; ENOG502QT0C; Eukaryota.
DR GeneTree; ENSGT00940000156055; -.
DR HOGENOM; CLU_011309_1_0_1; -.
DR InParanoid; P02788; -.
DR OMA; KSVRWCT; -.
DR OrthoDB; 559299at2759; -.
DR PhylomeDB; P02788; -.
DR TreeFam; TF324013; -.
DR PathwayCommons; P02788; -.
DR Reactome; R-HSA-1222449; Mtb iron assimilation by chelation.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6799990; Metal sequestration by antimicrobial proteins.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR Reactome; R-HSA-977225; Amyloid fiber formation.
DR SignaLink; P02788; -.
DR SIGNOR; P02788; -.
DR BioGRID-ORCS; 4057; 46 hits in 1078 CRISPR screens.
DR ChiTaRS; LTF; human.
DR EvolutionaryTrace; P02788; -.
DR GeneWiki; Lactoferrin; -.
DR GenomeRNAi; 4057; -.
DR Pharos; P02788; Tbio.
DR PRO; PR:P02788; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P02788; protein.
DR Bgee; ENSG00000012223; Expressed in trachea and 142 other tissues.
DR ExpressionAtlas; P02788; baseline and differential.
DR Genevisible; P02788; HS.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IMP:AgBase.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0097013; C:phagocytic vesicle lumen; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IBA:GO_Central.
DR GO; GO:0030141; C:secretory granule; IDA:MGI.
DR GO; GO:0042581; C:specific granule; IDA:UniProtKB.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:1904724; C:tertiary granule lumen; TAS:Reactome.
DR GO; GO:0004869; F:cysteine-type endopeptidase inhibitor activity; IDA:CAFA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IDA:UniProtKB.
DR GO; GO:0004252; F:serine-type endopeptidase activity; TAS:ProtInc.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0019732; P:antifungal humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IMP:UniProtKB.
DR GO; GO:0060349; P:bone morphogenesis; IDA:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0006959; P:humoral immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA: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:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0051673; P:membrane disruption in another organism; IMP:UniProtKB.
DR GO; GO:0044793; P:negative regulation by host of viral process; IMP:AgBase.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0032780; P:negative regulation of ATP-dependent activity; IMP:AgBase.
DR GO; GO:2000117; P:negative regulation of cysteine-type endopeptidase activity; IDA:CAFA.
DR GO; GO:0031665; P:negative regulation of lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0045837; P:negative regulation of membrane potential; IMP: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; IDA:UniProtKB.
DR GO; GO:2000308; P:negative regulation of tumor necrosis factor (ligand) superfamily member 11 production; ISS:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:AgBase.
DR GO; GO:0048525; P:negative regulation of viral process; IMP:AgBase.
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; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:UniProtKB.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IDA:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0001817; P:regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IDA:UniProtKB.
DR GO; GO:0001895; P:retina homeostasis; HEP:UniProtKB.
DR DisProt; DP00616; -.
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 3D-structure; Alternative promoter usage; Antibiotic; Antimicrobial;
KW Cytoplasm; Direct protein sequencing; Disulfide bond; DNA-binding;
KW Glycoprotein; Heparin-binding; Hydrolase; Immunity; Ion transport; Iron;
KW Iron transport; Isopeptide bond; Metal-binding; Nucleus; Osteogenesis;
KW Protease; Reference proteome; Repeat; Secreted; Serine protease; Signal;
KW Transcription; Transcription regulation; Transport; Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:14573629"
FT CHAIN 20..710
FT /note="Lactotransferrin"
FT /id="PRO_0000035732"
FT PEPTIDE 20..67
FT /note="Lactoferricin-H"
FT /id="PRO_0000422770"
FT PEPTIDE 171..201
FT /note="Kaliocin-1"
FT /id="PRO_0000035733"
FT PEPTIDE 338..343
FT /note="Lactoferroxin-A"
FT /id="PRO_0000035734"
FT PEPTIDE 543..547
FT /note="Lactoferroxin-B"
FT /id="PRO_0000035735"
FT PEPTIDE 680..686
FT /note="Lactoferroxin-C"
FT /id="PRO_0000035736"
FT DOMAIN 25..352
FT /note="Transferrin-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT DOMAIN 364..695
FT /note="Transferrin-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741"
FT REGION 20..29
FT /note="Bactericidal and antifungal activity"
FT REGION 20..24
FT /note="Critical for glycosaminoglycan, lipid A, lysozyme
FT and DNA binding"
FT REGION 21..22
FT /note="Important for full bactericidal and antifungal
FT activities"
FT REGION 39..49
FT /note="Bactericidal and antifungal activity"
FT REGION 39..49
FT /note="Interaction with lipopolysaccharide"
FT REGION 39..46
FT /note="Interaction with PspA"
FT REGION 46..51
FT /note="Involved in glycosaminoglycan binding"
FT REGION 57..58
FT /note="Interaction with PspA"
FT ACT_SITE 92
FT /evidence="ECO:0000305|PubMed:12535064"
FT ACT_SITE 278
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:12535064"
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
FT BINDING 136
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 140
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 142
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 143
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
FT BINDING 454
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
FT BINDING 480
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 484
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 486
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 487
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00741,
FT ECO:0000269|PubMed:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:11128996, ECO:0000269|PubMed:12450380,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8931543,
FT ECO:0000269|PubMed:9003186, ECO:0000269|Ref.71"
FT BINDING 547
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
FT BINDING 616
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:10089347, ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380, ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:17543335,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:8371268,
FT ECO:0000269|PubMed:8594202, ECO:0000269|PubMed:8703903,
FT ECO:0000269|PubMed:8931543, ECO:0000269|PubMed:9003186,
FT ECO:0000269|Ref.71"
FT SITE 23
FT /note="Interaction with PspA"
FT SITE 32
FT /note="Interaction with PspA"
FT SITE 229
FT /note="Important for iron binding"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15299444,
FT ECO:0000269|PubMed:15299793, ECO:0000269|PubMed:1581307,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:18780401,
FT ECO:0000269|PubMed:8069634, ECO:0000269|Ref.71"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15299793,
FT ECO:0000269|PubMed:1581307, ECO:0000269|PubMed:16201406,
FT ECO:0000269|PubMed:18780401, ECO:0000269|PubMed:19159218,
FT ECO:0000269|Ref.71"
FT CARBOHYD 642
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:18780401"
FT DISULFID 28..64
FT DISULFID 38..55
FT DISULFID 134..217
FT DISULFID 176..192
FT DISULFID 189..200
FT DISULFID 250..264
FT DISULFID 367..399
FT DISULFID 377..390
FT DISULFID 424..705
FT DISULFID 446..668
FT DISULFID 478..553
FT DISULFID 502..696
FT DISULFID 512..526
FT DISULFID 523..536
FT DISULFID 594..608
FT DISULFID 646..651
FT VAR_SEQ 1..44
FT /note="Missing (in isoform DeltaLf)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9122171"
FT /id="VSP_044308"
FT VARIANT 22
FT /note="R -> RR (associated with lower plasma lactoferrin
FT concentrations; dbSNP:rs10662431)"
FT /evidence="ECO:0000269|PubMed:11702692,
FT ECO:0000269|PubMed:14573629, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:22406253,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:2374734,
FT ECO:0000269|PubMed:2402455, ECO:0000269|Ref.10,
FT ECO:0000269|Ref.11, ECO:0000269|Ref.17, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.8, ECO:0000269|Ref.9"
FT /id="VAR_069298"
FT VARIANT 29
FT /note="A -> T (in dbSNP:rs1126477)"
FT /evidence="ECO:0000269|PubMed:11702692,
FT ECO:0000269|PubMed:14573629, ECO:0000269|PubMed:22900286,
FT ECO:0000269|PubMed:9873069, ECO:0000269|Ref.11,
FT ECO:0000269|Ref.8, ECO:0000269|Ref.9"
FT /id="VAR_013504"
FT VARIANT 47
FT /note="K -> R (decreased antibacterial activity against
FT Gram-positive bacteria; seems to reduce susceptibility to
FT localized juvenile periodontitis; associated with increased
FT plasma lactoferrin concentrations and possibly with
FT susceptibility to coronary artery stenosis;
FT dbSNP:rs1126478)"
FT /evidence="ECO:0000269|PubMed:11702692,
FT ECO:0000269|PubMed:14573629, ECO:0000269|PubMed:22406253,
FT ECO:0000269|PubMed:22900286, ECO:0000269|PubMed:9873069,
FT ECO:0000269|Ref.11, ECO:0000269|Ref.8, ECO:0000269|Ref.9"
FT /id="VAR_013505"
FT VARIANT 148
FT /note="I -> T (in dbSNP:rs1126479)"
FT /evidence="ECO:0000269|PubMed:2402455"
FT /id="VAR_013506"
FT VARIANT 422
FT /note="G -> C (in dbSNP:rs1042055)"
FT /evidence="ECO:0000269|PubMed:2402455, ECO:0000269|Ref.10"
FT /id="VAR_013507"
FT VARIANT 579
FT /note="E -> D (in dbSNP:rs2073495)"
FT /evidence="ECO:0000269|PubMed:11702692,
FT ECO:0000269|PubMed:16201406, ECO:0000269|PubMed:22900286,
FT ECO:0000269|PubMed:25946035, ECO:0000269|Ref.25,
FT ECO:0000269|Ref.9"
FT /id="VAR_013508"
FT MUTAGEN 20..23
FT /note="Missing: Abolishes binding to heparin, lipid A,
FT lysozyme and DNA."
FT /evidence="ECO:0000269|PubMed:9359845"
FT MUTAGEN 20..22
FT /note="Missing: Greatly impairs binding to heparin, lipid
FT A, lysozyme and DNA. Impairs antibacterial activity."
FT /evidence="ECO:0000269|PubMed:11179314"
FT MUTAGEN 20..21
FT /note="Missing: Impairs binding to heparin, lipid A,
FT lysozyme and DNA."
FT MUTAGEN 79
FT /note="D->S: Impairs iron binding and changes domain
FT closure."
FT /evidence="ECO:0000269|PubMed:8594202"
FT MUTAGEN 92
FT /note="K->A: Almost no protease activity."
FT /evidence="ECO:0000269|PubMed:12535064"
FT MUTAGEN 140
FT /note="R->D,E,S: Disrupts anion binding site and
FT destabilizes iron binding."
FT /evidence="ECO:0000269|PubMed:12037297,
FT ECO:0000269|PubMed:8931543"
FT MUTAGEN 229
FT /note="R->G,E: Destabilizes iron binding slightly."
FT /evidence="ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380"
FT MUTAGEN 229
FT /note="R->K,L: Destabilizes iron binding significantly."
FT /evidence="ECO:0000269|PubMed:10828980,
FT ECO:0000269|PubMed:12450380"
FT MUTAGEN 270
FT /note="P->V: No effect."
FT /evidence="ECO:0000269|PubMed:12535064"
FT MUTAGEN 272
FT /note="H->A,C,G,E,F,L,M,P,Q,T,Y: Destabilizes iron
FT binding."
FT /evidence="ECO:0000269|PubMed:9003186"
FT MUTAGEN 278
FT /note="S->A: No protease activity."
FT /evidence="ECO:0000269|PubMed:12535064"
FT CONFLICT 14
FT /note="L -> P (in Ref. 17; AAA58656)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="R -> S (in Ref. 14; AAH15822/AAH15823)"
FT /evidence="ECO:0000305"
FT CONFLICT 36
FT /note="T -> D (in Ref. 22; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 49
FT /note="R -> C (in Ref. 14; AAH22347)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="G -> C (in Ref. 14; AAH15823)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="L -> R (in Ref. 14; AAH22347)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="Missing (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="Missing (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 409..410
FT /note="DA -> NASVLMDSEGGFLAR (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 415
FT /note="G -> E (in Ref. 17; AAA59511)"
FT /evidence="ECO:0000305"
FT CONFLICT 431
FT /note="A -> G (in Ref. 17; AAA58656)"
FT /evidence="ECO:0000305"
FT CONFLICT 456
FT /note="A -> T (in Ref. 14; AAH15822/AAH15823)"
FT /evidence="ECO:0000305"
FT CONFLICT 487
FT /note="G -> A (in Ref. 26; AAA86665)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="Q -> E (in Ref. 18; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 537
FT /note="V -> E (in Ref. 14; AAH15822)"
FT /evidence="ECO:0000305"
FT CONFLICT 694
FT /note="K -> R (in Ref. 18; AA sequence and 27; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT STRAND 24..31
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 32..47
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:1Z6W"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 80..87
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 93..102
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 104..118
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:1LGB"
FT HELIX 125..127
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 141..144
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 145..151
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:1LCT"
FT HELIX 164..171
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 172..176
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 182..184
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 189..191
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:1N76"
FT HELIX 210..219
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 224..229
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 232..236
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 240..243
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 251..253
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 258..263
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 283..297
FT /evidence="ECO:0007829|PDB:1H45"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:1H45"
FT STRAND 325..328
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 335..339
FT /evidence="ECO:0007829|PDB:1H45"
FT HELIX 341..348
FT /evidence="ECO:0007829|PDB:1LFI"
FT HELIX 349..351
FT /evidence="ECO:0007829|PDB:1LFI"
FT HELIX 354..362
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 363..370
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 371..383
FT /evidence="ECO:0007829|PDB:1CB6"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 387..395
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 396..404
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 410..413
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 415..423
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 427..434
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 436..439
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:1B0L"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 454..463
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 469..471
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 475..480
FT /evidence="ECO:0007829|PDB:1CB6"
FT TURN 485..488
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 489..499
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 504..506
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 508..512
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:1LFI"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:1CB6"
FT TURN 533..536
FT /evidence="ECO:0007829|PDB:1LFH"
FT HELIX 546..555
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 560..565
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 566..570
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 573..576
FT /evidence="ECO:0007829|PDB:1LFI"
FT HELIX 580..583
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 587..589
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 590..593
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 599..601
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 602..607
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 610..613
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 617..620
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 622..624
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 625..639
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 640..642
FT /evidence="ECO:0007829|PDB:1N76"
FT TURN 646..649
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 655..657
FT /evidence="ECO:0007829|PDB:1CB6"
FT STRAND 666..670
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 678..682
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 684..696
FT /evidence="ECO:0007829|PDB:1CB6"
FT HELIX 700..709
FT /evidence="ECO:0007829|PDB:1CB6"
FT MOD_RES P02788-2:10
FT /note="Phosphoserine; alternate"
FT /evidence="ECO:0000269|PubMed:20404350"
FT CARBOHYD P02788-2:10
FT /note="O-linked (GlcNAc) serine; alternate"
FT /evidence="ECO:0000269|PubMed:20404350"
FT CROSSLNK P02788-2:379
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20404350"
FT CROSSLNK P02788-2:391
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:20404350"
SQ SEQUENCE 710 AA; 78182 MW; 0489CABA6D13C098 CRC64;
MKLVFLVLLF LGALGLCLAG RRRSVQWCAV SQPEATKCFQ WQRNMRKVRG PPVSCIKRDS
PIQCIQAIAE NRADAVTLDG GFIYEAGLAP YKLRPVAAEV YGTERQPRTH YYAVAVVKKG
GSFQLNELQG LKSCHTGLRR TAGWNVPIGT LRPFLNWTGP PEPIEAAVAR FFSASCVPGA
DKGQFPNLCR LCAGTGENKC AFSSQEPYFS YSGAFKCLRD GAGDVAFIRE STVFEDLSDE
AERDEYELLC PDNTRKPVDK FKDCHLARVP SHAVVARSVN GKEDAIWNLL RQAQEKFGKD
KSPKFQLFGS PSGQKDLLFK DSAIGFSRVP PRIDSGLYLG SGYFTAIQNL RKSEEEVAAR
RARVVWCAVG EQELRKCNQW SGLSEGSVTC SSASTTEDCI ALVLKGEADA MSLDGGYVYT
AGKCGLVPVL AENYKSQQSS DPDPNCVDRP VEGYLAVAVV RRSDTSLTWN SVKGKKSCHT
AVDRTAGWNI PMGLLFNQTG SCKFDEYFSQ SCAPGSDPRS NLCALCIGDE QGENKCVPNS
NERYYGYTGA FRCLAENAGD VAFVKDVTVL QNTDGNNNEA WAKDLKLADF ALLCLDGKRK
PVTEARSCHL AMAPNHAVVS RMDKVERLKQ VLLHQQAKFG RNGSDCPDKF CLFQSETKNL
LFNDNTECLA RLHGKTTYEK YLGPQYVAGI TNLKKCSTSP LLEACEFLRK
