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Protein

Lactotransferrin

Gene

LTF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transferrins are iron binding transport proteins which can bind two Fe3+ ions in association with the binding of an anion, usually bicarbonate.
Lactotransferrin is a major iron-binding and multifunctional protein found in exocrine fluids such as breast milk and mucosal secretions. Has antimicrobial activity, which depends on the extracellular cation concentration. Antimicrobial properties include bacteriostasis, which is related to its ability to sequester free iron and thus inhibit microbial growth, as well as direct bactericidal properties leading to the release of lipopolysaccharides from the bacterial outer membrane. Can also prevent bacterial biofilm development in P.aeruginosa infection. Has weak antifungal activity against C.albicans. Has anabolic, differentiating and anti-apoptotic effects on osteoblasts and can also inhibit osteoclastogenesis, possibly playing a role in the regulation of bone growth. Promotes binding of species C adenoviruses to epithelial cells, promoting adenovirus infection. Can inhibit papillomavirus infections. Stimulates the TLR4 signaling pathway leading to NF-kappa-B activation and subsequent pro-inflammatory cytokine production while also interfering with the lipopolysaccharide (LPS)-stimulated TLR4 signaling. Inhibits neutrophil granulocyte migration to sites of apoptosis, when secreted by apoptotic cells. Stimulates VEGFA-mediated endothelial cell migration and proliferation. Binds heparin, chondroitin sulfate and possibly other glycosaminoglycans (GAGs). Also binds specifically to pneumococcal surface protein A (pspA), the lipid A portion of bacterial lipopolysaccharide (LPS), lysozyme and DNA.
Lactoferricin binds to the bacterial surface and is crucial for the bactericidal functions. Has some antiviral activity against papillomavirus infection. N-terminal region shows strong antifungal activity against C.albicans. Contains two BBXB heparin-binding consensus sequences that appear to form the predominate functional GAG-binding site.
Kaliocin-1 has antimicrobial activity and is able to permeabilize different ions through liposomal membranes.
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.
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.
Isoform DeltaLf: transcription factor with antiproliferative properties and ability to induce cell cycle arrest. Binds to the DeltaLf response element found in the SKP1, BAX, DCPS, and SELH promoters.

Catalytic activityi

Preferential at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei23PspA1
Binding sitei32PspA1
Metal bindingi79Iron or copper 1PROSITE-ProRule annotation13 Publications1
Active sitei92Curated1
Metal bindingi111Iron or copper 1PROSITE-ProRule annotation13 Publications1
Binding sitei136Carbonate or oxalate 1PROSITE-ProRule annotation14 Publications1
Binding sitei140Carbonate or oxalate 1PROSITE-ProRule annotation14 Publications1
Binding sitei142Carbonate or oxalate 1; via amide nitrogenPROSITE-ProRule annotation14 Publications1
Binding sitei143Carbonate or oxalate 1; via amide nitrogenPROSITE-ProRule annotation14 Publications1
Metal bindingi211Iron or copper 1PROSITE-ProRule annotation13 Publications1
Sitei229Important for iron binding1
Metal bindingi272Iron or copper 1; via tele nitrogenPROSITE-ProRule annotation13 Publications1
Active sitei278NucleophileCurated1
Metal bindingi414Iron or copper 2PROSITE-ProRule annotation13 Publications1
Metal bindingi454Iron or copper 2PROSITE-ProRule annotation13 Publications1
Binding sitei480Carbonate or oxalate 2PROSITE-ProRule annotation14 Publications1
Binding sitei484Carbonate or oxalate 2PROSITE-ProRule annotation14 Publications1
Binding sitei486Carbonate or oxalate 2; via amide nitrogenPROSITE-ProRule annotation14 Publications1
Binding sitei487Carbonate or oxalate 2; via amide nitrogenPROSITE-ProRule annotation14 Publications1
Metal bindingi547Iron or copper 2PROSITE-ProRule annotation13 Publications1
Metal bindingi616Iron or copper 2; via tele nitrogenPROSITE-ProRule annotation13 Publications1

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • heparin binding Source: MGI
  • iron ion binding Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: UniProtKB
  • serine-type endopeptidase activity Source: ProtInc

GO - Biological processi

  • antibacterial humoral response Source: UniProtKB
  • antifungal humoral response Source: UniProtKB
  • bone morphogenesis Source: UniProtKB
  • cell redox homeostasis Source: Reactome
  • cellular protein metabolic process Source: Reactome
  • humoral immune response Source: ProtInc
  • innate immune response in mucosa Source: UniProtKB
  • ion transport Source: UniProtKB-KW
  • iron assimilation by chelation and transport Source: Reactome
  • negative regulation by host of viral process Source: AgBase
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of ATPase activity Source: AgBase
  • negative regulation of lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • negative regulation of osteoclast development Source: UniProtKB
  • negative regulation of single-species biofilm formation in or on host organism Source: UniProtKB
  • negative regulation of tumor necrosis factor (ligand) superfamily member 11 production Source: UniProtKB
  • negative regulation of viral genome replication Source: AgBase
  • negative regulation of viral process Source: AgBase
  • ossification Source: UniProtKB-KW
  • positive regulation of bone mineralization involved in bone maturation Source: UniProtKB
  • positive regulation of chondrocyte proliferation Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of osteoblast differentiation Source: UniProtKB
  • positive regulation of osteoblast proliferation Source: UniProtKB
  • positive regulation of protein serine/threonine kinase activity Source: UniProtKB
  • positive regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
  • regulation of cytokine production Source: UniProtKB
  • regulation of tumor necrosis factor production Source: UniProtKB
  • retina homeostasis Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Hydrolase, Protease, Serine protease

Keywords - Biological processi

Immunity, Ion transport, Iron transport, Osteogenesis, Transcription, Transcription regulation, Transport

Keywords - Ligandi

DNA-binding, Heparin-binding, Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000012223-MONOMER.
ReactomeiR-HSA-1222449. Mtb iron assimilation by chelation.
R-HSA-1222556. ROS, RNS production in response to bacteria.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.
R-HSA-6803157. Antimicrobial peptides.
R-HSA-977225. Amyloid fiber formation.
SIGNORiP02788.

Protein family/group databases

MEROPSiS60.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Lactotransferrin (EC:3.4.21.-)
Short name:
Lactoferrin
Alternative name(s):
Growth-inhibiting protein 12
Talalactoferrin
Cleaved into the following 5 chains:
Gene namesi
Name:LTF
Synonyms:GIG12, LF
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:6720. LTF.

Subcellular locationi

Isoform 1 :
  • Secreted
  • Cytoplasmic granule

  • Note: Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.
Isoform DeltaLf :

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: AgBase
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • nucleus Source: UniProtKB
  • phagocytic vesicle lumen Source: Reactome
  • protein complex Source: UniProtKB
  • secretory granule Source: MGI
  • specific granule Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi20 – 23Missing : Abolishes binding to heparin, lipid A, lysozyme and DNA. 1 Publication4
Mutagenesisi20 – 22Missing : Greatly impairs binding to heparin, lipid A, lysozyme and DNA. Impairs antibacterial activity. 1 Publication3
Mutagenesisi20 – 21Missing : Impairs binding to heparin, lipid A, lysozyme and DNA. 2
Mutagenesisi79D → S: Impairs iron binding and changes domain closure. 1 Publication1
Mutagenesisi92K → A: Almost no protease activity. 1 Publication1
Mutagenesisi140R → D, E or S: Disrupts anion binding site and destabilizes iron binding. 2 Publications1
Mutagenesisi229R → G or E: Destabilizes iron binding slightly. 2 Publications1
Mutagenesisi229R → K or L: Destabilizes iron binding significantly. 2 Publications1
Mutagenesisi270P → V: No effect. 1 Publication1
Mutagenesisi272H → A, C, G, E, F, L, M, P, Q, T or Y: Destabilizes iron binding. 1 Publication1
Mutagenesisi278S → A: No protease activity. 1 Publication1

Organism-specific databases

DisGeNETi4057.
MIMi245480. phenotype.
OpenTargetsiENSG00000012223.
PharmGKBiPA30482.

Protein family/group databases

Allergomei1384. Hom s LF.

Chemistry databases

DrugBankiDB04743. Nimesulide.
DB08439. Parecoxib.

Polymorphism and mutation databases

BioMutaiLTF.
DMDMi85700158.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 191 PublicationAdd BLAST19
ChainiPRO_000003573220 – 710LactotransferrinAdd BLAST691
PeptideiPRO_000042277020 – 67Lactoferricin-HAdd BLAST48
PeptideiPRO_0000035733171 – 201Kaliocin-1Add BLAST31
PeptideiPRO_0000035734338 – 343Lactoferroxin-A6
PeptideiPRO_0000035735543 – 547Lactoferroxin-B5
PeptideiPRO_0000035736680 – 686Lactoferroxin-C7

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi28 ↔ 64
Disulfide bondi38 ↔ 55
Disulfide bondi134 ↔ 217
Glycosylationi156N-linked (GlcNAc...)7 Publications1
Disulfide bondi176 ↔ 192
Disulfide bondi189 ↔ 200
Disulfide bondi250 ↔ 264
Disulfide bondi367 ↔ 399
Disulfide bondi377 ↔ 390
Disulfide bondi424 ↔ 705
Disulfide bondi446 ↔ 668
Disulfide bondi478 ↔ 553
Glycosylationi497N-linked (GlcNAc...)6 Publications1
Disulfide bondi502 ↔ 696
Disulfide bondi512 ↔ 526
Disulfide bondi523 ↔ 536
Disulfide bondi594 ↔ 608
Glycosylationi642N-linked (GlcNAc...)1 Publication1
Disulfide bondi646 ↔ 651
Isoform DeltaLf (identifier: P02788-2)
Modified residuei10Phosphoserine1 Publication1

Post-translational modificationi

Isoform DeltaLf: Ubiquitinated at Lys-379 and Lys-391.
Poly-N-acetyllactosaminic carbohydrate moiety seems to be needed for TLR4 activation.

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP02788.
PaxDbiP02788.
PeptideAtlasiP02788.
PRIDEiP02788.

PTM databases

iPTMnetiP02788.
PhosphoSitePlusiP02788.
UniCarbKBiP02788.

Expressioni

Tissue specificityi

High levels are found in saliva and tears, intermediate levels in serum and plasma, and low levels in urine. In kidney, detected in the distal collecting tubules in the medulla but not in the cortical region or in blood vessels. Detected in peripheral blood neutrophils (at protein level). Isoform 1 and isoform DeltaLf are expressed in breast, prostate, spleen, pancreas, kidney, small intestine, lung, skeletal muscle, uterus, thymus and fetal liver. Isoform 1 is expressed in brain, testis and peripheral blood leukocytes; isoform DeltaLf is barely detectable in these tissues. Isoform DeltaLf is expressed in placenta, liver and ovary; isoform 1 is barely detectable in these tissues. In kidney, isoform 1 is expressed at high levels in the collecting tubules of the medulla but at very low levels in the cortex.3 Publications

Gene expression databases

BgeeiENSG00000012223.
ExpressionAtlasiP02788. baseline and differential.
GenevisibleiP02788. HS.

Organism-specific databases

HPAiCAB008646.
CAB016201.
HPA057177.
HPA059976.

Interactioni

Subunit structurei

Monomer. Found in a complex with LTF, CLU, EPPIN and SEMG1.20 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
P279589EBI-1058602,EBI-6904269From a different organism.
CALMP621572EBI-1058602,EBI-397403From a different organism.

Protein-protein interaction databases

BioGridi110235. 32 interactors.
DIPiDIP-41354N.
IntActiP02788. 10 interactors.
MINTiMINT-1511753.
STRINGi9606.ENSP00000231751.

Structurei

Secondary structure

1710
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi24 – 31Combined sources8
Helixi32 – 47Combined sources16
Beta strandi50 – 52Combined sources3
Beta strandi53 – 57Combined sources5
Helixi61 – 69Combined sources9
Beta strandi75 – 78Combined sources4
Helixi80 – 87Combined sources8
Turni89 – 91Combined sources3
Beta strandi93 – 102Combined sources10
Beta strandi104 – 118Combined sources15
Beta strandi119 – 121Combined sources3
Helixi125 – 127Combined sources3
Beta strandi132 – 136Combined sources5
Turni141 – 144Combined sources4
Helixi145 – 151Combined sources7
Helixi152 – 154Combined sources3
Turni159 – 161Combined sources3
Helixi164 – 171Combined sources8
Beta strandi172 – 176Combined sources5
Turni182 – 184Combined sources3
Helixi186 – 188Combined sources3
Turni189 – 191Combined sources3
Helixi196 – 198Combined sources3
Beta strandi206 – 208Combined sources3
Helixi210 – 219Combined sources10
Beta strandi224 – 229Combined sources6
Helixi232 – 236Combined sources5
Helixi240 – 243Combined sources4
Beta strandi246 – 250Combined sources5
Turni251 – 253Combined sources3
Beta strandi254 – 257Combined sources4
Helixi258 – 263Combined sources6
Beta strandi266 – 270Combined sources5
Beta strandi273 – 280Combined sources8
Helixi283 – 297Combined sources15
Turni299 – 301Combined sources3
Beta strandi317 – 319Combined sources3
Beta strandi325 – 328Combined sources4
Helixi335 – 339Combined sources5
Helixi341 – 348Combined sources8
Helixi349 – 351Combined sources3
Helixi354 – 362Combined sources9
Beta strandi363 – 370Combined sources8
Helixi371 – 383Combined sources13
Turni384 – 386Combined sources3
Beta strandi387 – 395Combined sources9
Helixi396 – 404Combined sources9
Beta strandi410 – 413Combined sources4
Helixi415 – 423Combined sources9
Beta strandi427 – 434Combined sources8
Beta strandi436 – 439Combined sources4
Beta strandi440 – 442Combined sources3
Helixi446 – 448Combined sources3
Beta strandi454 – 463Combined sources10
Helixi469 – 471Combined sources3
Beta strandi475 – 480Combined sources6
Turni485 – 488Combined sources4
Helixi489 – 499Combined sources11
Helixi504 – 506Combined sources3
Beta strandi508 – 512Combined sources5
Beta strandi514 – 516Combined sources3
Helixi521 – 523Combined sources3
Turni533 – 536Combined sources4
Helixi546 – 555Combined sources10
Beta strandi560 – 565Combined sources6
Helixi566 – 570Combined sources5
Beta strandi573 – 576Combined sources4
Helixi580 – 583Combined sources4
Helixi587 – 589Combined sources3
Beta strandi590 – 593Combined sources4
Beta strandi599 – 601Combined sources3
Helixi602 – 607Combined sources6
Beta strandi610 – 613Combined sources4
Beta strandi617 – 620Combined sources4
Helixi622 – 624Combined sources3
Helixi625 – 639Combined sources15
Beta strandi640 – 642Combined sources3
Turni646 – 649Combined sources4
Beta strandi655 – 657Combined sources3
Beta strandi666 – 670Combined sources5
Helixi678 – 682Combined sources5
Helixi684 – 696Combined sources13
Helixi700 – 709Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B0LX-ray2.20A20-710[»]
1BKAX-ray2.40A20-710[»]
1CB6X-ray2.00A20-710[»]
1DSNX-ray2.05A21-352[»]
1EH3X-ray2.00A21-352[»]
1FCKX-ray2.20A21-710[»]
1H43X-ray2.20A21-352[»]
1H44X-ray2.00A21-352[»]
1H45X-ray1.95A21-352[»]
1HSEX-ray2.20A21-353[»]
1L5TX-ray3.00A/B21-351[»]
1LCFX-ray2.00A20-710[»]
1LCTX-ray2.00A21-352[»]
1LFGX-ray2.20A20-710[»]
1LFHX-ray2.80A20-710[»]
1LFIX-ray2.10A20-710[»]
1LGBX-ray3.30C110-268[»]
1N76X-ray3.40A21-710[»]
1SQYX-ray2.50A20-710[»]
1U62NMR-A39-44[»]
1VFDX-ray2.50A20-349[»]
1VFEX-ray2.30A20-352[»]
1XV4NMR-A39-44[»]
1XV7NMR-A39-44[»]
1Z6VNMR-A21-67[»]
1Z6WNMR-A21-67[»]
2BJJX-ray2.40X21-710[»]
2DP4X-ray2.90I528-535[»]
2GMCNMR-A39-44[»]
2GMDNMR-A39-44[»]
2HD4X-ray2.15B528-535[»]
2PMSX-ray2.91A/B21-362[»]
DisProtiDP00616.
ProteinModelPortaliP02788.
SMRiP02788.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP02788.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini25 – 352Transferrin-like 1PROSITE-ProRule annotationAdd BLAST328
Domaini364 – 695Transferrin-like 2PROSITE-ProRule annotationAdd BLAST332

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 29Bactericidal and antifungal activity10
Regioni20 – 24Critical for glycosaminoglycan, lipid A, lysozyme and DNA binding5
Regioni21 – 22Important for full bactericidal and antifungal activities2
Regioni39 – 49Bactericidal and antifungal activityAdd BLAST11
Regioni39 – 49Interaction with lipopolysaccharideAdd BLAST11
Regioni39 – 46Interaction with pspA8
Regioni46 – 51Involved in glycosaminoglycan binding6
Regioni57 – 58Interaction with pspA2

Sequence similaritiesi

Belongs to the transferrin family.PROSITE-ProRule annotation
Contains 2 transferrin-like domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IEAI. Eukaryota.
ENOG410XQ36. LUCA.
GeneTreeiENSGT00390000001619.
HOVERGENiHBG000055.
InParanoidiP02788.
KOiK17283.
OMAiRPVEGYL.
OrthoDBiEOG091G0242.
PhylomeDBiP02788.
TreeFamiTF324013.

Family and domain databases

InterProiIPR030684. Lactotransferrin.
IPR016357. Transferrin.
IPR001156. Transferrin-like_dom.
IPR018195. Transferrin_Fe_BS.
[Graphical view]
PfamiPF00405. Transferrin. 2 hits.
[Graphical view]
PIRSFiPIRSF500683. Lactotransferrin. 1 hit.
PIRSF002549. Transferrin. 1 hit.
PRINTSiPR00422. TRANSFERRIN.
SMARTiSM00094. TR_FER. 2 hits.
[Graphical view]
PROSITEiPS00205. 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]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: P02788-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKLVFLVLLF LGALGLCLAG RRRSVQWCAV SQPEATKCFQ WQRNMRKVRG
60 70 80 90 100
PPVSCIKRDS PIQCIQAIAE NRADAVTLDG GFIYEAGLAP YKLRPVAAEV
110 120 130 140 150
YGTERQPRTH YYAVAVVKKG GSFQLNELQG LKSCHTGLRR TAGWNVPIGT
160 170 180 190 200
LRPFLNWTGP PEPIEAAVAR FFSASCVPGA DKGQFPNLCR LCAGTGENKC
210 220 230 240 250
AFSSQEPYFS YSGAFKCLRD GAGDVAFIRE STVFEDLSDE AERDEYELLC
260 270 280 290 300
PDNTRKPVDK FKDCHLARVP SHAVVARSVN GKEDAIWNLL RQAQEKFGKD
310 320 330 340 350
KSPKFQLFGS PSGQKDLLFK DSAIGFSRVP PRIDSGLYLG SGYFTAIQNL
360 370 380 390 400
RKSEEEVAAR RARVVWCAVG EQELRKCNQW SGLSEGSVTC SSASTTEDCI
410 420 430 440 450
ALVLKGEADA MSLDGGYVYT AGKCGLVPVL AENYKSQQSS DPDPNCVDRP
460 470 480 490 500
VEGYLAVAVV RRSDTSLTWN SVKGKKSCHT AVDRTAGWNI PMGLLFNQTG
510 520 530 540 550
SCKFDEYFSQ SCAPGSDPRS NLCALCIGDE QGENKCVPNS NERYYGYTGA
560 570 580 590 600
FRCLAENAGD VAFVKDVTVL QNTDGNNNEA WAKDLKLADF ALLCLDGKRK
610 620 630 640 650
PVTEARSCHL AMAPNHAVVS RMDKVERLKQ VLLHQQAKFG RNGSDCPDKF
660 670 680 690 700
CLFQSETKNL LFNDNTECLA RLHGKTTYEK YLGPQYVAGI TNLKKCSTSP
710
LLEACEFLRK
Length:710
Mass (Da):78,182
Last modified:January 24, 2006 - v6
Checksum:i0489CABA6D13C098
GO
Isoform DeltaLf (identifier: P02788-2) [UniParc]FASTAAdd to basket
Also known as: Delta-lactoferrin

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

Note: 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.1 Publication
Show »
Length:666
Mass (Da):73,161
Checksum:iC498CC5861CA1A12
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti14L → P in AAA58656 (Ref. 17) Curated1
Sequence conflicti21R → S in AAH15822 (PubMed:15489334).Curated1
Sequence conflicti21R → S in AAH15823 (PubMed:15489334).Curated1
Sequence conflicti36T → D AA sequence (PubMed:8551695).Curated1
Sequence conflicti49R → C in AAH22347 (PubMed:15489334).Curated1
Sequence conflicti130G → C in AAH15823 (PubMed:15489334).Curated1
Sequence conflicti138L → R in AAH22347 (PubMed:15489334).Curated1
Sequence conflicti140Missing AA sequence (PubMed:6510420).Curated1
Sequence conflicti169Missing AA sequence (PubMed:6510420).Curated1
Sequence conflicti409 – 410DA → NASVLMDSEGGFLAR AA sequence (PubMed:6510420).Curated2
Sequence conflicti415G → E in AAA59511 (Ref. 17) Curated1
Sequence conflicti431A → G in AAA58656 (Ref. 17) Curated1
Sequence conflicti456A → T in AAH15822 (PubMed:15489334).Curated1
Sequence conflicti456A → T in AAH15823 (PubMed:15489334).Curated1
Sequence conflicti487G → A in AAA86665 (PubMed:3477300).Curated1
Sequence conflicti531Q → E AA sequence (PubMed:6510420).Curated1
Sequence conflicti537V → E in AAH15822 (PubMed:15489334).Curated1
Sequence conflicti694K → R AA sequence (PubMed:6510420).Curated1
Sequence conflicti694K → R AA sequence (PubMed:7049727).Curated1

Mass spectrometryi

Molecular mass is 5737.8 Da from positions 20 - 67. Determined by ESI. 1 Publication

Polymorphismi

The sequence shown corresponds to the reference genome sequence and is likely to represent the minor allele, whereas most publications refer to the longer sequence containing variant Arg-22 ins. Insertion of the additional arginine in variant Arg-22 ins creates an N-terminal basic cluster of four arginines, all of which appear to be important for the full functionality of the protein, including bactericidal and antifungal activities as well as binding to glycosaminoglycans, pspA, LPS, lysozyme and DNA.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06929822R → RR Associated with lower plasma lactoferrin concentrations. 14 PublicationsCorresponds to variant rs10662431dbSNPEnsembl.1
Natural variantiVAR_01350429A → T.7 PublicationsCorresponds to variant rs1126477dbSNPEnsembl.1
Natural variantiVAR_01350547K → R Decreased antibacterial activity against Gram-positive bacteria; seems to reduce susceptibility to localized juvenile periodontitis; associated with increased plasma lactoferrin concentrations and possibly with susceptibility to coronary artery stenosis. 8 PublicationsCorresponds to variant rs1126478dbSNPEnsembl.1
Natural variantiVAR_013506148I → T.1 PublicationCorresponds to variant rs1126479dbSNPEnsembl.1
Natural variantiVAR_013507422G → C.2 PublicationsCorresponds to variant rs1042055dbSNPEnsembl.1
Natural variantiVAR_013508579E → D.6 PublicationsCorresponds to variant rs2073495dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0443081 – 44Missing in isoform DeltaLf. 2 PublicationsAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53961 mRNA. Translation: CAA37914.1.
U07643 mRNA. Translation: AAB60324.1.
AF332168 mRNA. Translation: AAG48753.1.
AY178998 mRNA. Translation: AAN75578.2.
AY137470 mRNA. Translation: AAN11304.1.
M73700 Genomic DNA. Translation: AAA59479.1.
M93150 mRNA. Translation: AAA36159.1.
AY165046 mRNA. Translation: AAN63998.1.
AY493417 mRNA. Translation: AAS72878.1.
EU622050 Genomic DNA. Translation: ACC95966.1.
AK292813 mRNA. Translation: BAF85502.1.
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.
M83202 mRNA. Translation: AAA59511.1.
M83205 mRNA. Translation: AAA58656.1.
U95626 Genomic DNA. Translation: AAB57795.1.
M18642 mRNA. Translation: AAA86665.1.
CCDSiCCDS33747.1. [P02788-1]
CCDS56251.1. [P02788-2]
PIRiG01394. TFHUL.
RefSeqiNP_001186078.1. NM_001199149.1. [P02788-2]
NP_001308050.1. NM_001321121.1.
NP_001308051.1. NM_001321122.1.
NP_002334.2. NM_002343.5. [P02788-1]
UniGeneiHs.529517.

Genome annotation databases

EnsembliENST00000231751; ENSP00000231751; ENSG00000012223. [P02788-1]
ENST00000426532; ENSP00000405719; ENSG00000012223. [P02788-2]
GeneIDi4057.
KEGGihsa:4057.
UCSCiuc003fzr.4. human. [P02788-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Lactotransferrin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X53961 mRNA. Translation: CAA37914.1.
U07643 mRNA. Translation: AAB60324.1.
AF332168 mRNA. Translation: AAG48753.1.
AY178998 mRNA. Translation: AAN75578.2.
AY137470 mRNA. Translation: AAN11304.1.
M73700 Genomic DNA. Translation: AAA59479.1.
M93150 mRNA. Translation: AAA36159.1.
AY165046 mRNA. Translation: AAN63998.1.
AY493417 mRNA. Translation: AAS72878.1.
EU622050 Genomic DNA. Translation: ACC95966.1.
AK292813 mRNA. Translation: BAF85502.1.
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.
M83202 mRNA. Translation: AAA59511.1.
M83205 mRNA. Translation: AAA58656.1.
U95626 Genomic DNA. Translation: AAB57795.1.
M18642 mRNA. Translation: AAA86665.1.
CCDSiCCDS33747.1. [P02788-1]
CCDS56251.1. [P02788-2]
PIRiG01394. TFHUL.
RefSeqiNP_001186078.1. NM_001199149.1. [P02788-2]
NP_001308050.1. NM_001321121.1.
NP_001308051.1. NM_001321122.1.
NP_002334.2. NM_002343.5. [P02788-1]
UniGeneiHs.529517.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B0LX-ray2.20A20-710[»]
1BKAX-ray2.40A20-710[»]
1CB6X-ray2.00A20-710[»]
1DSNX-ray2.05A21-352[»]
1EH3X-ray2.00A21-352[»]
1FCKX-ray2.20A21-710[»]
1H43X-ray2.20A21-352[»]
1H44X-ray2.00A21-352[»]
1H45X-ray1.95A21-352[»]
1HSEX-ray2.20A21-353[»]
1L5TX-ray3.00A/B21-351[»]
1LCFX-ray2.00A20-710[»]
1LCTX-ray2.00A21-352[»]
1LFGX-ray2.20A20-710[»]
1LFHX-ray2.80A20-710[»]
1LFIX-ray2.10A20-710[»]
1LGBX-ray3.30C110-268[»]
1N76X-ray3.40A21-710[»]
1SQYX-ray2.50A20-710[»]
1U62NMR-A39-44[»]
1VFDX-ray2.50A20-349[»]
1VFEX-ray2.30A20-352[»]
1XV4NMR-A39-44[»]
1XV7NMR-A39-44[»]
1Z6VNMR-A21-67[»]
1Z6WNMR-A21-67[»]
2BJJX-ray2.40X21-710[»]
2DP4X-ray2.90I528-535[»]
2GMCNMR-A39-44[»]
2GMDNMR-A39-44[»]
2HD4X-ray2.15B528-535[»]
2PMSX-ray2.91A/B21-362[»]
DisProtiDP00616.
ProteinModelPortaliP02788.
SMRiP02788.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110235. 32 interactors.
DIPiDIP-41354N.
IntActiP02788. 10 interactors.
MINTiMINT-1511753.
STRINGi9606.ENSP00000231751.

Chemistry databases

DrugBankiDB04743. Nimesulide.
DB08439. Parecoxib.

Protein family/group databases

Allergomei1384. Hom s LF.
MEROPSiS60.001.

PTM databases

iPTMnetiP02788.
PhosphoSitePlusiP02788.
UniCarbKBiP02788.

Polymorphism and mutation databases

BioMutaiLTF.
DMDMi85700158.

Proteomic databases

EPDiP02788.
PaxDbiP02788.
PeptideAtlasiP02788.
PRIDEiP02788.

Protocols and materials databases

DNASUi4057.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000231751; ENSP00000231751; ENSG00000012223. [P02788-1]
ENST00000426532; ENSP00000405719; ENSG00000012223. [P02788-2]
GeneIDi4057.
KEGGihsa:4057.
UCSCiuc003fzr.4. human. [P02788-1]

Organism-specific databases

CTDi4057.
DisGeNETi4057.
GeneCardsiLTF.
HGNCiHGNC:6720. LTF.
HPAiCAB008646.
CAB016201.
HPA057177.
HPA059976.
MIMi150210. gene.
245480. phenotype.
neXtProtiNX_P02788.
OpenTargetsiENSG00000012223.
PharmGKBiPA30482.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEAI. Eukaryota.
ENOG410XQ36. LUCA.
GeneTreeiENSGT00390000001619.
HOVERGENiHBG000055.
InParanoidiP02788.
KOiK17283.
OMAiRPVEGYL.
OrthoDBiEOG091G0242.
PhylomeDBiP02788.
TreeFamiTF324013.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000012223-MONOMER.
ReactomeiR-HSA-1222449. Mtb iron assimilation by chelation.
R-HSA-1222556. ROS, RNS production in response to bacteria.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-6799990. Metal sequestration by antimicrobial proteins.
R-HSA-6803157. Antimicrobial peptides.
R-HSA-977225. Amyloid fiber formation.
SIGNORiP02788.

Miscellaneous databases

ChiTaRSiLTF. human.
EvolutionaryTraceiP02788.
GeneWikiiLactoferrin.
GenomeRNAii4057.
PROiP02788.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000012223.
ExpressionAtlasiP02788. baseline and differential.
GenevisibleiP02788. HS.

Family and domain databases

InterProiIPR030684. Lactotransferrin.
IPR016357. Transferrin.
IPR001156. Transferrin-like_dom.
IPR018195. Transferrin_Fe_BS.
[Graphical view]
PfamiPF00405. Transferrin. 2 hits.
[Graphical view]
PIRSFiPIRSF500683. Lactotransferrin. 1 hit.
PIRSF002549. Transferrin. 1 hit.
PRINTSiPR00422. TRANSFERRIN.
SMARTiSM00094. TR_FER. 2 hits.
[Graphical view]
PROSITEiPS00205. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiTRFL_HUMAN
AccessioniPrimary (citable) accession number: P02788
Secondary accession number(s): A8K9U8
, B2MV13, B7Z4X2, E7EQH5, O00756, Q16780, Q16785, Q16786, Q16789, Q5DSM0, Q8IU92, Q8IZH6, Q8TCD2, Q96KZ4, Q96KZ5, Q9H1Z3, Q9UCY5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 24, 2006
Last modified: November 30, 2016
This is version 209 of the entry and version 6 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.