Platelet factor 4

PF4
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RHP, 1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 4R9W, 4R9Y, 4RAU
Identifiers
Aliases	PF4, CXCL4, PF-4, SCYB4, platelet factor 4
External IDs	OMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4
Gene ontology Molecular function • cytokine activity • heparin binding • CXCR3 chemokine receptor binding • chemokine activity Cellular component • extracellular fluid • extracellular region • platelet alpha granule lumen Biological process • G-protein coupled receptor signaling pathway • positive regulation of cAMP metabolic process • cytokine-mediated signaling pathway • chemokine-mediated signaling pathway • positive regulation of macrophage differentiation • platelet degranulation • negative regulation of megakaryocyte differentiation • positive regulation of cAMP-mediated signaling • negative regulation of MHC class II biosynthetic process • leukocyte chemotaxis • chemotaxis • positive regulation of leukocyte chemotaxis • response to lipopolysaccharide • positive regulation of macrophage derived foam cell differentiation • positive regulation of gene expression • regulation of cell proliferation • immune response • positive regulation of tumor necrosis factor production • negative regulation of angiogenesis • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • inflammatory response • positive regulation of transcription from RNA polymerase II promoter • negative regulation of cytolysis • platelet activation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5196	56744
Ensembl	ENSG00000163737	ENSMUSG00000029373
UniProt	P02776	Q9Z126
RefSeq (mRNA)	NM_002619	NM_019932
RefSeq (protein)	NP_002610.1	NP_064316.1
Location (UCSC)	Chr 4: 73.98 – 73.98 Mb	Chr 5: 90.77 – 90.77 Mb
PubMed search	[1]	[2]
Wikidata

Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.^[3] It is usually found in a complex with proteoglycan.

Genomics

The gene for human PF4 is located on human chromosome 4.^[4]

Function

Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.^[3][5]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.^[6]

Clinical significance

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.^[7] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.^[8]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.^[9]

See also

• Platelet-activating factor
• Platelet-derived growth factor

References

1. ↑ "Human PubMed Reference:". 
2. ↑ "Mouse PubMed Reference:". 
3. 1 2 Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (July 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood. 76 (2): 336–44. PMID 1695112. 
4. ↑ O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098. 
5. ↑ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)". 
6. ↑ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". J Exp Med. 197 (11): 1537–1549. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716. 
7. ↑ Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. doi:10.1056/NEJMp068309. PMID 17329695. 
8. ↑ Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060. 
9. ↑ Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, Degrado WF, Sinnis P, Scott RW, Greenbaum DC (December 2012). "Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials". Cell Host Microbe. 12 (6): 815–23. doi:10.1016/j.chom.2012.10.017. PMID 23245326. 

Further reading

External links

• Platelet factor 4 at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery
1f9q: CRYSTAL STRUCTURE OF PLATELET FACTOR 4  1f9r: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 1  1f9s: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 2  1pfm: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 1-15 OF A 27-MODEL SET.  1pfn: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 16-27 OF A 27-MODEL SET.  1rhp: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLATELET FACTOR 4

This article incorporates text from the United States National Library of Medicine, which is in the public domain.