P02788 (TRFL_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lactotransferrin
Short name=Lactoferrin
EC=3.4.21.-

Alternative name(s):
Talalactoferrin

Cleaved into the following 4 chains:

1. Kaliocin-1
2. Lactoferroxin-A
3. Lactoferroxin-B
4. Lactoferroxin-C

Gene names

Name:	LTF
Synonyms:	LF

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	710 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transferrins are iron binding transport proteins which can bind two Fe3+ ions in association with the binding of an anion, usually bicarbonate. Ref.23 Ref.29 Lactotransferrin has antimicrobial activity which depends on the extracellular cation concentration. Ref.23 Ref.29 Lactoferroxins A, B and C have opioid antagonist activity. Lactoferroxin A shows preference for mu-receptors, while lactoferroxin B and C have somewhat higher degrees of preference for kappa-receptors than for mu-receptors. Ref.23 Ref.29 The lactotransferrin transferrin-like domain 1 functions as a serine protease of the peptidase S60 family that cuts arginine rich regions. This function contributes to the antimicrobial activity. Ref.23 Ref.29 Isoform DeltaLf: transcription factor with antiproliferative properties and inducing cell cycle arrest. Binds to DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters. Ref.23 Ref.29
Catalytic activity	Preferential at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin.
Subunit structure	Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1. Ref.24
Subcellular location	Isoform 1: Secreted. Isoform DeltaLf: Cytoplasm. Nucleus.
Post-translational modification	Isoform DeltaLf: Ubiquitinated at Lys-379 and Lys-391. Ref.27
Sequence similarities	Belongs to the transferrin family. Contains 2 transferrin-like domains.

Ontologies

Keywords
Biological process	Ion transport Iron transport Transcription Transcription regulation Transport
Cellular component	Cytoplasm Nucleus Secreted
Coding sequence diversity	Alternative promoter usage Polymorphism
Domain	Repeat Signal
Ligand	DNA-binding Iron Metal-binding
Molecular function	Antibiotic Antimicrobial Hydrolase Protease Serine protease
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW humoral immune response Traceable author statement PubMed 9770539. Source: ProtInc iron assimilation by chelation and transport Traceable author statement. Source: Reactome iron ion transport Inferred from electronic annotation. Source: InterPro phagosome maturation Traceable author statement. Source: Reactome proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to host immune response Traceable author statement. Source: Reactome transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	extracellular region Traceable author statement. Source: Reactome nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell phagocytic vesicle lumen Traceable author statement. Source: Reactome secretory granule Inferred from direct assay PubMed 11907569. Source: MGI
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW ferric iron binding Inferred from electronic annotation. Source: InterPro heparin binding Inferred from direct assay PubMed 11907569. Source: MGI serine-type endopeptidase activity Traceable author statement PubMed 9770539. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CALM	P62157	2	EBI-1058602,EBI-397403	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform 1 (identifier: P02788-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform DeltaLf (identifier: P02788-2)

Also known as: Delta-lactoferrin;

The sequence of this isoform differs from the canonical sequence as follows:
     1-44: Missing.

Note: Phosphorylated at Ser-10. Glycosylated at Ser-10. O-GlcNAcylation at Ser-10 inhibits DNA binding and negatively regulates DeltaLf transcriptional activity, whereas phosphorylation activates it. Phosphorylation at Ser-10 also promotes proteasomal degradation.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.15 Ref.16 Ref.17

Chain

20 – 710

691

Lactotransferrin

PRO_0000035732

Peptide

171 – 201

31

Kaliocin-1

PRO_0000035733

Peptide

338 – 343

6

Lactoferroxin-A

PRO_0000035734

Peptide

543 – 547

5

Lactoferroxin-B

PRO_0000035735

Peptide

680 – 686

7

Lactoferroxin-C

PRO_0000035736

Regions

Domain

25 – 352

328

Transferrin-like 1

Domain

364 – 695

332

Transferrin-like 2

Sites

Active site

92

1

Probable

Active site

278

1

Nucleophile Probable

Metal binding

79

1

Iron 1

Metal binding

111

1

Iron 1

Metal binding

211

1

Iron 1

Metal binding

272

1

Iron 1

Metal binding

414

1

Iron 2

Metal binding

454

1

Iron 2

Metal binding

547

1

Iron 2

Metal binding

616

1

Iron 2

Binding site

136

1

Carbonate 1

Binding site

140

1

Carbonate 1

Binding site

142

1

Carbonate 1; via amide nitrogen

Binding site

143

1

Carbonate 1; via amide nitrogen

Binding site

480

1

Carbonate 2

Binding site

484

1

Carbonate 2

Binding site

486

1

Carbonate 2; via amide nitrogen

Binding site

487

1

Carbonate 2; via amide nitrogen

Amino acid modifications

Glycosylation

156

1

N-linked (GlcNAc...) Ref.25

Glycosylation

497

1

N-linked (GlcNAc...) Ref.25 Ref.26

Glycosylation

642

1

N-linked (GlcNAc...) Ref.25

Disulfide bond

28 ↔ 64

Disulfide bond

38 ↔ 55

Disulfide bond

134 ↔ 217

Disulfide bond

176 ↔ 192

Disulfide bond

189 ↔ 200

Disulfide bond

250 ↔ 264

Disulfide bond

367 ↔ 399

Disulfide bond

377 ↔ 390

Disulfide bond

424 ↔ 705

Disulfide bond

446 ↔ 668

Disulfide bond

478 ↔ 553

Disulfide bond

502 ↔ 696

Disulfide bond

512 ↔ 526

Disulfide bond

523 ↔ 536

Disulfide bond

594 ↔ 608

Disulfide bond

646 ↔ 651

Natural variations

Alternative sequence

1 – 44

44

Missing in isoform DeltaLf.

VSP_044308

Natural variant

29

1

A → T. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.35
Corresponds to variant rs1126477 [ dbSNP | Ensembl ].

VAR_013504

Natural variant

47

1

K → R. Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.35
Corresponds to variant rs1126478 [ dbSNP | Ensembl ].

VAR_013505

Natural variant

148

1

I → T. Ref.1
Corresponds to variant rs1126479 [ dbSNP | Ensembl ].

VAR_013506

Natural variant

422

1

G → C. Ref.1
Corresponds to variant rs1042055 [ dbSNP | Ensembl ].

VAR_013507

Natural variant

579

1

E → D. Ref.6 Ref.8 Ref.9 Ref.20
Corresponds to variant rs2073495 [ dbSNP | Ensembl ].

VAR_013508

Experimental info

Mutagenesis

92

1

K → A: Almost no protease activity. Ref.23

Mutagenesis

270

1

P → V: No effect. Ref.23

Mutagenesis

278

1

S → A: No protease activity. Ref.23

Sequence conflict

14

1

L → P in AAA58656. Ref.4

Sequence conflict

20

1

G → GS in AAH15822. Ref.12

Sequence conflict

20

1

G → GS in AAH15823. Ref.12

Sequence conflict

23

1

R → RR in CAA37914. Ref.1

Sequence conflict

23

1

R → RR in AAB60324. Ref.2

Sequence conflict

23

1

R → RR in AAA36159. Ref.3

Sequence conflict

23

1

R → RR in AAA59511. Ref.4

Sequence conflict

23

1

R → RR in AAA58656. Ref.4

Sequence conflict

23

1

R → RR in AAG48753. Ref.6

Sequence conflict

23

1

R → RR in AAN11304. Ref.7

Sequence conflict

23

1

R → RR in AAN63998. Ref.8

Sequence conflict

23

1

R → RR in AAN75578. Ref.9

Sequence conflict

23

1

R → RR in AAH22347. Ref.12

Sequence conflict

23

1

R → RR in CAA37116. Ref.14

Sequence conflict

36

1

T → D AA sequence Ref.17

Sequence conflict

49

1

R → C in AAH22347. Ref.12

Sequence conflict

130

1

G → C in AAH15823. Ref.12

Sequence conflict

138

1

L → R in AAH22347. Ref.12

Sequence conflict

140

1

Missing AA sequence Ref.15

Sequence conflict

169

1

Missing AA sequence Ref.15

Sequence conflict

409 – 410

2

DA → NASVLMDSEGGFLAR AA sequence Ref.15

Sequence conflict

415

1

G → E in AAA59511. Ref.4

Sequence conflict

431

1

A → G in AAA58656. Ref.4

Sequence conflict

456

1

A → T in AAH15822. Ref.12

Sequence conflict

456

1

A → T in AAH15823. Ref.12

Sequence conflict

487

1

G → A in AAA86665. Ref.19

Sequence conflict

531

1

Q → E AA sequence Ref.15

Sequence conflict

537

1

V → E in AAH15822. Ref.12

Sequence conflict

694

1

K → R AA sequence Ref.15

Sequence conflict

694

1

K → R AA sequence Ref.18

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

710

Helix Strand Turn

Details...

Beta strand

24 – 31

8

Helix

32 – 47

16

Beta strand

50 – 52

3

Beta strand

53 – 57

5

Helix

61 – 69

9

Beta strand

75 – 78

4

Helix

80 – 87

8

Turn

89 – 91

3

Beta strand

93 – 102

10

Beta strand

104 – 118

15

Beta strand

119 – 121

3

Helix

125 – 127

3

Beta strand

132 – 136

5

Turn

141 – 144

4

Helix

145 – 151

7

Helix

152 – 154

3

Turn

159 – 161

3

Helix

164 – 171

8

Beta strand

172 – 176

5

Turn

182 – 184

3

Helix

186 – 188

3

Turn

189 – 191

3

Helix

196 – 198

3

Beta strand

206 – 208

3

Helix

210 – 219

10

Beta strand

224 – 229

6

Helix

232 – 236

5

Helix

240 – 243

4

Beta strand

246 – 250

5

Turn

251 – 253

3

Beta strand

254 – 257

4

Helix

258 – 263

6

Beta strand

266 – 270

5

Beta strand

273 – 280

8

Helix

283 – 297

15

Turn

299 – 301

3

Beta strand

317 – 319

3

Beta strand

325 – 328

4

Helix

335 – 339

5

Helix

341 – 348

8

Helix

349 – 351

3

Helix

354 – 362

9

Beta strand

363 – 370

8

Helix

371 – 383

13

Turn

384 – 386

3

Beta strand

387 – 395

9

Helix

396 – 404

9

Beta strand

410 – 413

4

Helix

415 – 423

9

Beta strand

427 – 434

8

Beta strand

436 – 439

4

Beta strand

440 – 442

3

Helix

446 – 448

3

Beta strand

454 – 463

10

Helix

469 – 471

3

Beta strand

475 – 480

6

Turn

485 – 488

4

Helix

489 – 499

11

Helix

504 – 506

3

Beta strand

508 – 512

5

Beta strand

514 – 516

3

Helix

521 – 523

3

Turn

533 – 536

4

Helix

546 – 555

10

Beta strand

560 – 565

6

Helix

566 – 570

5

Beta strand

573 – 576

4

Helix

580 – 583

4

Helix

587 – 589

3

Beta strand

590 – 593

4

Beta strand

599 – 601

3

Helix

602 – 607

6

Beta strand

610 – 613

4

Beta strand

617 – 620

4

Helix

622 – 624

3

Helix

625 – 639

15

Beta strand

640 – 642

3

Turn

646 – 649

4

Beta strand

655 – 657

3

Beta strand

666 – 670

5

Helix

678 – 682

5

Helix

684 – 696

13

Helix

700 – 709

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2006. Version 6. Checksum: 0489CABA6D13C098	FASTA	710	78,182
	10 20 30 40 50 60 MKLVFLVLLF LGALGLCLAG RRRSVQWCAV SQPEATKCFQ WQRNMRKVRG PPVSCIKRDS 70 80 90 100 110 120 PIQCIQAIAE NRADAVTLDG GFIYEAGLAP YKLRPVAAEV YGTERQPRTH YYAVAVVKKG 130 140 150 160 170 180 GSFQLNELQG LKSCHTGLRR TAGWNVPIGT LRPFLNWTGP PEPIEAAVAR FFSASCVPGA 190 200 210 220 230 240 DKGQFPNLCR LCAGTGENKC AFSSQEPYFS YSGAFKCLRD GAGDVAFIRE STVFEDLSDE 250 260 270 280 290 300 AERDEYELLC PDNTRKPVDK FKDCHLARVP SHAVVARSVN GKEDAIWNLL RQAQEKFGKD 310 320 330 340 350 360 KSPKFQLFGS PSGQKDLLFK DSAIGFSRVP PRIDSGLYLG SGYFTAIQNL RKSEEEVAAR 370 380 390 400 410 420 RARVVWCAVG EQELRKCNQW SGLSEGSVTC SSASTTEDCI ALVLKGEADA MSLDGGYVYT 430 440 450 460 470 480 AGKCGLVPVL AENYKSQQSS DPDPNCVDRP VEGYLAVAVV RRSDTSLTWN SVKGKKSCHT 490 500 510 520 530 540 AVDRTAGWNI PMGLLFNQTG SCKFDEYFSQ SCAPGSDPRS NLCALCIGDE QGENKCVPNS 550 560 570 580 590 600 NERYYGYTGA FRCLAENAGD VAFVKDVTVL QNTDGNNNEA WAKDLKLADF ALLCLDGKRK 610 620 630 640 650 660 PVTEARSCHL AMAPNHAVVS RMDKVERLKQ VLLHQQAKFG RNGSDCPDKF CLFQSETKNL 670 680 690 700 710 LFNDNTECLA RLHGKTTYEK YLGPQYVAGI TNLKKCSTSP LLEACEFLRK
	Isoform DeltaLf (Delta-lactoferrin) [UniParc]. Checksum: C498CC5861CA1A12	FASTA	666	73,161
	10 20 30 40 50 60 MRKVRGPPVS CIKRDSPIQC IQAIAENRAD AVTLDGGFIY EAGLAPYKLR PVAAEVYGTE 70 80 90 100 110 120 RQPRTHYYAV AVVKKGGSFQ LNELQGLKSC HTGLRRTAGW NVPIGTLRPF LNWTGPPEPI 130 140 150 160 170 180 EAAVARFFSA SCVPGADKGQ FPNLCRLCAG TGENKCAFSS QEPYFSYSGA FKCLRDGAGD 190 200 210 220 230 240 VAFIRESTVF EDLSDEAERD EYELLCPDNT RKPVDKFKDC HLARVPSHAV VARSVNGKED 250 260 270 280 290 300 AIWNLLRQAQ EKFGKDKSPK FQLFGSPSGQ KDLLFKDSAI GFSRVPPRID SGLYLGSGYF 310 320 330 340 350 360 TAIQNLRKSE EEVAARRARV VWCAVGEQEL RKCNQWSGLS EGSVTCSSAS TTEDCIALVL 370 380 390 400 410 420 KGEADAMSLD GGYVYTAGKC GLVPVLAENY KSQQSSDPDP NCVDRPVEGY LAVAVVRRSD 430 440 450 460 470 480 TSLTWNSVKG KKSCHTAVDR TAGWNIPMGL LFNQTGSCKF DEYFSQSCAP GSDPRSNLCA 490 500 510 520 530 540 LCIGDEQGEN KCVPNSNERY YGYTGAFRCL AENAGDVAFV KDVTVLQNTD GNNNEAWAKD 550 560 570 580 590 600 LKLADFALLC LDGKRKPVTE ARSCHLAMAP NHAVVSRMDK VERLKQVLLH QQAKFGRNGS 610 620 630 640 650 660 DCPDKFCLFQ SETKNLLFND NTECLARLHG KTTYEKYLGP QYVAGITNLK KCSTSPLLEA CEFLRK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Complete nucleotide sequence of human mammary gland lactoferrin." Rey M.W., Woloshuk S.L., de Boer H.A., Pieper F.R. Nucleic Acids Res. 18:5288-5288(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-148 AND CYS-422. Tissue: Mammary gland.
[2]	Cho Y.Y. Thesis (1994), Genetic Engineering Research Institute, South Korea Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Mammary gland.
[3]	Conneely O.M. Submitted (MAY-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-29 AND ARG-47.
[4]	"Molecular cloning and sequence analysis of human lactoferrin." Liang Q., Jimenez-Flores R., Richardson T. Submitted (DEC-1991) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Mammary gland.
[5]	"Human neutrophil lactoferrin coding and 5' flanking region DNA sequences." Wei X., Han J., Rado T.A. Submitted (FEB-1992) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Tissue: Bone marrow.
[6]	"cDNA cloning and sequence analysis of human lactoferrin." Cheng H., Chen X.Z., Huan L.D. Sheng Wu Gong Cheng Xue Bao 17:385-387(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-29; ARG-47 AND ASP-579. Tissue: Mammary gland.
[7]	"Characterization of an amino acid polymorphism in the antibacterial domain of human lactoferrin." Kaplan J.B., Fine D.H. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-29 AND ARG-47.
[8]	Shi Y.-Q., Zhang Y., Zheng Y.-M. Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-29; ARG-47 AND ASP-579. Tissue: Mammary gland.
[9]	Baskar Singh S., Saravanan K., Paramasivam M., Srinivasan A., Singh T.P. Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS THR-29; ARG-47 AND ASP-579. Tissue: Seminal vesicle.
[10]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM DELTALF). Tissue: Lung.
[11]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Prostate.
[13]	"Differential molecular mechanism of the estrogen action that regulates lactoferrin gene in human and mouse." Teng C.T., Liu Y., Yang N., Walmer D., Panella T. Mol. Endocrinol. 6:1969-1981(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[14]	"Nucleotide sequence of human lactoferrin cDNA." Powell M.J., Ogden J.E. Nucleic Acids Res. 18:4013-4013(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-710 (ISOFORM DELTALF). Tissue: Mammary gland.
[15]	"Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins." Metz-Boutigue M.-H., Jolles J., Mazurier J., Schoentgen F., Legrand D., Spik G., Montreuil J., Jolles P. Eur. J. Biochem. 145:659-676(1984) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-710.
[16]	"The present state of the human lactotransferrin sequence. Study and alignment of the cyanogen bromide fragments and characterization of N- and C-terminal domains." Metz-Boutigue M.-H., Mazurier J., Jolles J., Spik G., Montreuil J., Jolles P. Biochim. Biophys. Acta 670:243-254(1981) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 20-72; 133-170; 256-277 AND 346-529.
[17]	"Characterization of the 84-kDa protein with ABH activity in human seminal plasma." Sato I. Nihon Hoigaku Zasshi 49:281-293(1995) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-56. Tissue: Seminal plasma.
[18]	"An 88 amino acid long C-terminal sequence of human lactotransferrin." Metz-Boutigue M.-H., Jolles J., Mazurier J., Spik G., Montreuil J., Jolles P. FEBS Lett. 142:107-110(1982) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 608-710.
[19]	"Isolation of lactoferrin cDNA from a human myeloid library and expression of mRNA during normal and leukemic myelopoiesis." Rado T.A., Wei X., Benz E.J. Jr. Blood 70:989-993(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 435-710.
[20]	McCombie W.R., Wilson R., Chen E., Gibbs R., Zuo L., Johnson D., Nhan M., Parnell L., Dedhia N., Ansari A., Mardis E., Schutz K., Gnoj L., la Bastide M., Kaplan N., Greco T., Touchman J., Muzny D. , Chen C.N., Evans C., Fitzgerald M., See L.H., Tang M., Porcel B.M., Dragan Y., Giacalone J., Pae A., Powell E., Solinsky K.A., Desilva U., Diaz-Perez S., Zhou X., Yu Y., Watanabe M., Doggett N., Garcia D., Sagripanti J.L. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 236-710, VARIANT ASP-579.
[21]	"Isolation and characterization of opioid antagonist peptides derived from human lactoferrin." Tani F., Iio K., Chiba H., Yoshikawa M. Agric. Biol. Chem. 54:1803-1810(1990) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF LACTOFERROXINS.
[22]	"Potassium efflux induced by a new lactoferrin-derived peptide mimicking the effect of native human lactoferrin on the bacterial cytoplasmic membrane." Viejo-Diaz M., Andres M.T., Perez-Gil J., Sanchez M., Fierro J.F. Biokhimiia 68:217-227(2003) [PubMed] [Europe PMC] [Abstract] Cited for: SYNTHESIS OF 171-201 (KALIOCIN-1).
[23]	"Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites." Hendrixson D.R., Qiu J., Shewry S.C., Fink D.L., Petty S., Baker E.N., Plaut A.G., St Geme J.W. III Mol. Microbiol. 47:607-617(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A PROTEASE, MUTAGENESIS OF LYS-92; PRO-270 AND SER-278.
[24]	"Characterization of an eppin protein complex from human semen and spermatozoa." Wang Z., Widgren E.E., Richardson R.T., O'Rand M.G. Biol. Reprod. 77:476-484(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH CLU; SEMG1 AND EPPIN.
[25]	"Identification of N-linked glycoproteins in human milk by hydrophilic interaction liquid chromatography and mass spectrometry." Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F. Proteomics 8:3833-3847(2008) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156; ASN-497 AND ASN-642, MASS SPECTROMETRY. Tissue: Milk.
[26]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-497, MASS SPECTROMETRY. Tissue: Liver.
[27]	"O-GlcNAcylation/phosphorylation cycling at Ser10 controls both transcriptional activity and stability of delta-lactoferrin." Hardiville S., Hoedt E., Mariller C., Benaissa M., Pierce A. J. Biol. Chem. 285:19205-19218(2010) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION, PHOSPHORYLATION, UBIQUITINATION (ISOFORM DELTALF).
[28]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]	"Delta-lactoferrin, an intracellular lactoferrin isoform that acts as a transcription factor." Mariller C., Hardiville S., Hoedt E., Huvent I., Pina-Canseco S., Pierce A. Biochem. Cell Biol. 90:307-319(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A TRANSCRIPTION FACTOR (ISOFORM DELTALF), DNA-BINDING (ISOFORM DELTALF).
[30]	"Structure of human lactoferrin: crystallographic structure analysis and refinement at 2.8-A resolution." Anderson B.F., Baker H.M., Norris G.E., Rice D.W., Baker E.N. J. Mol. Biol. 209:711-734(1989) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), SEQUENCE REVISION.
[31]	"Structure of human diferric lactoferrin refined at 2.2-A resolution." Haridas M., Anderson B.F., Baker E.N. Acta Crystallogr. D 51:629-646(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[32]	"Mutagenesis of the histidine ligand in human lactoferrin: iron binding properties and crystal structure of the histidine-253-->methionine mutant." Nicholson H., Anderson B.F., Bland T., Shewry S.C., Tweedie J.W., Baker E.N. Biochemistry 36:341-346(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-352.
[33]	"Structure of recombinant human lactoferrin expressed in Aspergillus awamori." Sun X.L., Baker H.M., Shewry S.C., Jameson G.B., Baker E.N. Acta Crystallogr. D 55:403-407(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[34]	"Structure of human apolactoferrin at 2.0-A resolution. Refinement and analysis of ligand-induced conformational change." Jameson G.B., Anderson B.F., Norris G.E., Thomas D.H., Baker E.N. Acta Crystallogr. D 54:1319-1335(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[35]	"Familial subepithelial corneal amyloidosis (gelatinous drop-like corneal dystrophy): exclusion of linkage to lactoferrin gene." Klintworth G.K., Sommer J.R., Obrian G., Han L., Ahmed M.N., Qumsiyeh M.B., Lin P.-Y., Basti S., Reddy M.K., Kanai A., Hotta Y., Sugar J., Kumaramanickavel G., Munier F., Schorderet D.F., El Matri L., Iwata F., Kaiser-Kupfer M. , Nagata M., Nakayasu K., Hejtmancik J.F., Teng C.T. Mol. Vis. 4:31-32(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS THR-29 AND ARG-47.
+	Additional computationally mapped references.

Web resources

Wikipedia

Lactotransferrin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X53961 mRNA. Translation: CAA37914.1.
U07643 mRNA. Translation: AAB60324.1.
M93150 mRNA. Translation: AAA36159.1.
M83202 mRNA. Translation: AAA59511.1.
M83205 mRNA. Translation: AAA58656.1.
M73700 Genomic DNA. Translation: AAA59479.1.
AF332168 mRNA. Translation: AAG48753.1.
AY137470 mRNA. Translation: AAN11304.1.
AY165046 mRNA. Translation: AAN63998.1.
AY178998 mRNA. Translation: AAN75578.2.
AK298035 mRNA. Translation: BAH12708.1.
AC098613 Genomic DNA. No translation available.
BC015822 mRNA. Translation: AAH15822.1.
BC015823 mRNA. Translation: AAH15823.1.
BC022347 mRNA. Translation: AAH22347.1.
S52659 Genomic DNA. Translation: AAB24877.1.
X52941 mRNA. Translation: CAA37116.1.
M18642 mRNA. Translation: AAA86665.1.
U95626 Genomic DNA. Translation: AAB57795.1.

IPI

IPI00298860.

PIR

TFHUL. G01394.

RefSeq

NP_001186078.1. NM_001199149.1.
NP_002334.2. NM_002343.3.

UniGene

Hs.529517.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B0L	X-ray	2.20	A	20-710	[»]
1BKA	X-ray	2.40	A	20-710	[»]
1CB6	X-ray	2.00	A	20-710	[»]
1DSN	X-ray	2.05	A	21-352	[»]
1EH3	X-ray	2.00	A	21-348	[»]
1FCK	X-ray	2.20	A	21-710	[»]
1H43	X-ray	2.20	A	21-352	[»]
1H44	X-ray	2.00	A	21-352	[»]
1H45	X-ray	1.95	A	21-352	[»]
1HSE	X-ray	2.20	A	21-353	[»]
1L5T	X-ray	3.00	A/B	21-351	[»]
1LCF	X-ray	2.00	A	20-710	[»]
1LCT	X-ray	2.00	A	21-352	[»]
1LFG	X-ray	2.20	A	20-710	[»]
1LFH	X-ray	2.80	A	20-710	[»]
1LFI	X-ray	2.10	A	20-710	[»]
1LGB	X-ray	3.30	C	110-268	[»]
1N76	X-ray	3.40	A	21-710	[»]
1SQY	X-ray	2.50	A	20-710	[»]
1U62	NMR	-	A	39-49	[»]
1VFD	X-ray	2.50	A	22-349	[»]
1VFE	X-ray	2.30	A	22-352	[»]
1XV4	NMR	-	A	39-49	[»]
1XV7	NMR	-	A	39-49	[»]
1Z6V	NMR	-	A	21-67	[»]
1Z6W	NMR	-	A	21-67	[»]
2BJJ	X-ray	2.40	X	21-710	[»]
2DP4	X-ray	2.90	I	528-535	[»]
2GMC	NMR	-	A	39-49	[»]
2GMD	NMR	-	A	39-49	[»]
2HD4	X-ray	2.15	B	528-535	[»]
2PMS	X-ray	2.91	A/B	21-362	[»]

ProteinModelPortal

P02788.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-41354N.

IntAct

P02788. 5 interactions.

MINT

MINT-1511753.

Protein family/group databases

Allergome

1384. Hom s Lactoferrin.

MEROPS

S60.001.

PTM databases

GlycoSuiteDB

P02788.

PhosphoSite

P02788.

Polymorphism databases

DMDM

85700158.

Proteomic databases

PaxDb

P02788.

PRIDE

P02788.

Protocols and materials databases

DNASU

4057.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000231751; ENSP00000231751; ENSG00000012223.
ENST00000426532; ENSP00000405719; ENSG00000012223.

GeneID

4057.

KEGG

hsa:4057.

UCSC

uc003cpq.3. human.

Organism-specific databases

CTD

4057.

GeneCards

GC03M046452.

HGNC

HGNC:6720. LTF.

HPA

CAB008645.

MIM

150210. gene.
245480. phenotype.

neXtProt

NX_P02788.

PharmGKB

PA30482.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG87503.

HOVERGEN

HBG000055.

InParanoid

P02788.

OMA

RPVEGYL.

OrthoDB

EOG4CRKZG.

PhylomeDB

P02788.

Enzyme and pathway databases

Reactome

REACT_116125. Disease.

Gene expression databases

ArrayExpress

P02788.

Bgee

P02788.

Genevestigator

P02788.

GermOnline

ENSG00000012223. Homo sapiens.

Family and domain databases

InterPro

IPR016357. Transferrin.
IPR001156. Transferrin_fam.
IPR018195. Transferrin_Fe_BS.
[Graphical view]

PANTHER

PTHR11485. PTHR11485. 1 hit.

Pfam

PF00405. Transferrin. 2 hits.
[Graphical view]

PIRSF

PIRSF002549. Transferrin. 1 hit.

PRINTS

PR00422. TRANSFERRIN.

SMART

SM00094. TR_FER. 2 hits.
[Graphical view]

PROSITE

PS00205. TRANSFERRIN_LIKE_1. 2 hits.
PS00206. TRANSFERRIN_LIKE_2. 2 hits.
PS00207. TRANSFERRIN_LIKE_3. 2 hits.
PS51408. TRANSFERRIN_LIKE_4. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

LTF. human.

DrugBank

DB00487. Pefloxacin.

EvolutionaryTrace

P02788.

GenomeRNAi

4057.

NextBio

15896.

SOURCE

Search...

Entry information

Entry name

TRFL_HUMAN

Accession

Primary (citable) accession number: P02788
Secondary accession number(s): B7Z4X2 , E7EQH5, O00756, Q16780, Q16785, Q16786, Q16789, Q8IU92, Q8IZH6, Q8TCD2, Q96KZ4, Q96KZ5, Q9H1Z3, Q9UCY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 24, 2006
Last modified:	May 29, 2013
This is version 170 of the entry and version 6 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.