TRFL_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: TRFL_HUMAN
• UniProt AC: P02788
• Protein Name: Lactotransferrin
• Gene Name: LTF
• Organism: Homo sapiens (Human).
• Sequence Length: 710
• Subcellular Localization: Isoform 1: Secreted. Cytoplasmic granule. Secreted into most exocrine fluids by various endothelial cells. Stored in the secondary granules of neutrophils.; Isoform DeltaLf: Cytoplasm. Nucleus. Mainly localized in the cytoplasm.
• Protein Description: Transferrins are iron binding transport proteins which can bind two Fe(3+) 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. Shows a preferential cleavage at -Arg-Ser-Arg-Arg-|- and -Arg-Arg-Ser-Arg-|-, and of Z-Phe-Arg-|-aminomethylcoumarin sites.; 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 SELENOH promoters..
• Protein Sequence: MKLVFLVLLFLGALGLCLAGRRRSVQWCAVSQPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLRDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAARRARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSQQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPRSNLCALCIGDEQGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
10 (in isoform 2)	O-linked_Glycosylation	-	5.31	20404350
10 (in isoform 2)	Phosphorylation	-	5.31	20404350
24	Phosphorylation	CLAGRRRSVQWCAVS HHCCCCCCCEEEEEC	19.49	28348404
54	O-linked_Glycosylation	KVRGPPVSCIKRDSP HCCCCCCHHCCCCCH	18.85	20404350
54	Phosphorylation	KVRGPPVSCIKRDSP HCCCCCCHHCCCCCH	18.85	20404350
57	Sumoylation	GPPVSCIKRDSPIQC CCCCHHCCCCCHHHH	55.25	-
57	Sumoylation	GPPVSCIKRDSPIQC CCCCHHCCCCCHHHH	55.25	-
111	Phosphorylation	ERQPRTHYYAVAVVK CCCCCCEEEEEEEEE	7.78	-
112	Phosphorylation	RQPRTHYYAVAVVKK CCCCCEEEEEEEEEC	6.23	-
122	Phosphorylation	AVVKKGGSFQLNELQ EEEECCCEEECCCCC	20.63	20068231
156	N-linked_Glycosylation	GTLRPFLNWTGPPEP CCCCCCCCCCCCCCH	34.34	1581307
156	N-linked_Glycosylation	GTLRPFLNWTGPPEP CCCCCCCCCCCCCCH	34.34	1581307
211	Phosphorylation	SQEPYFSYSGAFKCL CCCCCCCCCHHHHHH	10.96	22817900
216	Acetylation	FSYSGAFKCLRDGAG CCCCHHHHHHHCCCC	31.65	7825973
278	Phosphorylation	SHAVVARSVNGKEDA CCEEEEECCCCHHHH	15.36	20058876
320	Acetylation	GQKDLLFKDSAIGFS CCCCEEECCCCCCCC	51.23	25038526
327	Phosphorylation	KDSAIGFSRVPPRID CCCCCCCCCCCCCCC	27.44	24732914
352	Sumoylation	TAIQNLRKSEEEVAA HHHHHHHCCHHHHHH	66.44	-
352	Sumoylation	TAIQNLRKSEEEVAA HHHHHHHCCHHHHHH	66.44	-
405	Sumoylation	DCIALVLKGEADAMS HEEEEECCCCCCEEE	47.42	-
405	Sumoylation	DCIALVLKGEADAMS HEEEEECCCCCCEEE	47.42	-
423	Ubiquitination	GYVYTAGKCGLVPVL CEEEECCCCCCHHHH	23.75	-
423	Sumoylation	GYVYTAGKCGLVPVL CEEEECCCCCCHHHH	23.75	-
423	Sumoylation	GYVYTAGKCGLVPVL CEEEECCCCCCHHHH	23.75	-
435	Sumoylation	PVLAENYKSQQSSDP HHHHHHHCCCCCCCC	54.06	-
435	Sumoylation	PVLAENYKSQQSSDP HHHHHHHCCCCCCCC	54.06	-
435	Acetylation	PVLAENYKSQQSSDP HHHHHHHCCCCCCCC	54.06	133059
454	Phosphorylation	VDRPVEGYLAVAVVR CCCCCCCEEEEEEEE	4.31	-
477	Phosphorylation	NSVKGKKSCHTAVDR ECCCCCCCCCCCCCC	18.02	-
480	Phosphorylation	KGKKSCHTAVDRTAG CCCCCCCCCCCCCCC	32.48	-
485	Phosphorylation	CHTAVDRTAGWNIPM CCCCCCCCCCCCCCC	25.67	-
497	N-linked_Glycosylation	IPMGLLFNQTGSCKF CCCCCEECCCCCCCH	38.17	1581307
497	N-linked_Glycosylation	IPMGLLFNQTGSCKF CCCCCEECCCCCCCH	38.17	1581307
499	Phosphorylation	MGLLFNQTGSCKFDE CCCEECCCCCCCHHH	31.97	-
501	Phosphorylation	LLFNQTGSCKFDEYF CEECCCCCCCHHHHH	19.95	-
540	Phosphorylation	ENKCVPNSNERYYGY CCCCCCCCCCCCCCC	33.72	27251275
544	Phosphorylation	VPNSNERYYGYTGAF CCCCCCCCCCCCHHH	8.61	26330541
545	Phosphorylation	PNSNERYYGYTGAFR CCCCCCCCCCCHHHH	15.18	27251275
547	Phosphorylation	SNERYYGYTGAFRCL CCCCCCCCCHHHHHH	5.96	25884760
565	Acetylation	AGDVAFVKDVTVLQN CCCEEEEEEEEEEEC	39.77	88829
568	Phosphorylation	VAFVKDVTVLQNTDG EEEEEEEEEEECCCC	26.15	23403867
573	Phosphorylation	DVTVLQNTDGNNNEA EEEEEECCCCCCCCH	32.11	23403867
603	Phosphorylation	DGKRKPVTEARSCHL CCCCCCCCCHHHCCE	32.24	24719451
607	Phosphorylation	KPVTEARSCHLAMAP CCCCCHHHCCEECCC	16.97	24719451
608	S-nitrosylation	PVTEARSCHLAMAPN CCCCHHHCCEECCCC	2.25	25040305
620	Phosphorylation	APNHAVVSRMDKVER CCCCHHHCCHHHHHH	18.45	24719451
642	N-linked_Glycosylation	QQAKFGRNGSDCPDK HHHHHCCCCCCCCCC	55.49	18780401
642	N-linked_Glycosylation	QQAKFGRNGSDCPDK HHHHHCCCCCCCCCC	55.49	18780401
680	Acetylation	HGKTTYEKYLGPQYV CCCCCHHHHHCHHHE	35.05	25038526

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of TRFL_HUMAN !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
10	S	Phosphorylation	Alternatively can undergo phosphorylation at Ser-10.	20404350
10	S	Phosphorylation	Phosphorylation at Ser-10 also promotes proteasomal degradation.	20404350
10	S	Phosphorylation	[Isoform DeltaLf]: Phosphorylation at Ser-10 activates the transcriptional activity.	20404350

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
54	O-linked Glycosylation	47 (7)	K ⇒ R	rs1126478	Blood protein levels	28240269

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MUC7_HUMAN	MUC7	physical	12766201
LYSC_HUMAN	LYZ	physical	9359845
CD14_HUMAN	CD14	physical	11083760

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

N-linked Glycosylation

"Glycoproteomics analysis of human liver tissue by combination ofmultiple 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).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-497, AND MASSSPECTROMETRY.
PubMed: 19159218

"Identification of N-linked glycoproteins in human milk by hydrophilicinteraction liquid chromatography and mass spectrometry.";
Picariello G., Ferranti P., Mamone G., Roepstorff P., Addeo F.;
Proteomics 8:3833-3847(2008).
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-156; ASN-497 AND ASN-642,AND MASS SPECTROMETRY.
PubMed: 18780401

Phosphorylation

"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-547, AND MASSSPECTROMETRY.
PubMed: 18083107