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 location (Human)
Chr.	Chromosome 4 (human)[1]
End	73,982,027 bp[1]
Gene location (Mouse)
Chr.	Chromosome 5 (mouse)[2]
End	90,773,383 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• cytokine activity; • heparin binding; • CXCR3 chemokine receptor binding; • chemokine activity; • GO:0001948 protein binding;
Cellular component	• extracellular region; • platelet alpha granule lumen; • extracellular; • cytoplasm; • collagen-containing extracellular matrix;
Biological 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; • 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; • defense response; • positive regulation of neutrophil chemotaxis; • antimicrobial humoral immune response mediated by antimicrobial peptide; • regulation of megakaryocyte differentiation; • regulation of receptor activity; • G-protein coupled receptor signaling pathway; • adenylate cyclase-activating G-protein coupled receptor signaling pathway; • neutrophil chemotaxis; • cellular response to lipopolysaccharide;
	Sources:Amigo / QuickGO
Orthologs
	5196
	56744
	ENSG00000163737
	ENSMUSG00000029373
	P02776
	Q9Z126
	NM_002619; NM_001363352
	NM_019932
	NP_002610; NP_001350281
	NP_064316
	Wikidata
View/Edit Human	View/Edit Mouse

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.[5] It is usually found in a complex with proteoglycan.

Genomics

The gene for human PF4 is located on human chromosome 4.[6]

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 activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.[5][7]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.[8]

Clinical significance

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.[9] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[10]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.[11]

The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[12]

References

GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000029373 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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. doi:10.1182/blood.V76.2.336.336. PMID 1695112.
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. S2CID 8087808.
"Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".
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.
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.
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.
Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, Mayes M, Charles J, Tseng CH, Elashoff RM, Assassi S (2016). "Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease". Arthritis Research & Therapy. 18 (1): 305. doi:10.1186/s13075-016-1203-y. PMC 5203703. PMID 28038680.
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. PMC 3638032. PMID 23245326.

External links

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

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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000029373 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Eisman_1990-5] 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. doi:10.1182/blood.V76.2.336.336. PMID 1695112.

[6] 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. S2CID 8087808.

[7] "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".

[8] 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.

[9] 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.

[10] 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.

[11] Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, Mayes M, Charles J, Tseng CH, Elashoff RM, Assassi S (2016). "Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease". Arthritis Research & Therapy. 18 (1): 305. doi:10.1186/s13075-016-1203-y. PMC 5203703. PMID 28038680.

[pmid23245326-12] 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. PMC 3638032. PMID 23245326.