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FLASH GENE

Symbol

PF4

contributors: mct - updated : 25-01-2016

HGNC name	platelet factor 4
HGNC id	8861

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Homo sapiens Lymphoid/Immune lymphocyte Homo sapiens

cell lineage	expressed during megakaryocytic differentiation
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , tetramer

HOMOLOGY

interspecies

homolog to C.elegans F39H12.2

Homologene

FAMILY	platelet factor 4 family
	intercrine alpha family (small cytokine C-X-C) (chemokine CXC)

CATEGORY

signaling cytokine

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	released from the alpha-granules of activated platelets
	stored in secretory granules and released in response to protein kinase C activation

basic FUNCTION	neutralizing the anticoagulant effect of heparin because it binds more strongly to heparin than to chondroitin-4-sulfate chains of the carrier molecule
	chemotactic for neutrophils and monocytes
	released during platelet aggregation
	first chemokine described to inhibit neovascularization
	can protect hematopoiesis from chemotherapy by enhancing cell viability and suppress tumor growth through anti-angiogenic pathway
	playing a role in the modulation of monocyte-dependent T cell activation
	potent inhibitor of tumor-induced angiogenesis
	platelet-derived chemokine that promotes macrophage differentiation from monocyte
	chemokine that binds to and neutralizes heparin and other negatively charged proteoglycans, but is also involved in angiogenesis and cancer development
	(PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (ACKR1) are necessary for platelet-mediated killing of Plasmodium falciparum parasites
	important mechanistic role for platelets and PF4 in vascular smooth muscle cell injury responses
	regulates hematopoietic stem cells (HSCs) cycle activity
	plays several roles in coagulation, angiogenesis control, immune system modulation and spread of cancer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

immunity/defense

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	binding noncovalently to a proteoglycan molecule
	binding to heparin with high affinity
	interacting with integrin (integrins as novel receptors for PF4 that may contribute to its antiangiogenic effect)
	may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin
	in contrast to stimulation of protein C activation, PF4 is shown here to inhibit activation of CPB2 by thrombin-THBD
	FLI1, ELF1, and GABPA regulate PF4 gene expression through the -51 ETS site in megakaryocytes and implicate the differentiation stage-specific regulation of PF4 gene expression by multiple ETS factors
	function in killing plasmodium for PF4 is critically dependent on ACKR1, which binds PF4
	genetic disruption of ACKR1 expression inhibits binding of PF4 to parasitized cells and concomitantly prevents parasite killing by both human platelets and recombinant human PF4
	RUNX1 activates endogenous PF4 expression in megakaryocytic differentiation

cell & other

REGULATION

activated by

PREP1 and PREP1/PBX complexes with GATA-1 and ETS-1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in early growth of liposarcoma, mammary adenocarcinoma, and osteosarcoma

Susceptibility

Variant & Polymorphism

Candidate gene	potential biomarker of early tumor presence
Marker
Therapy target	several PF4 fragments and modified molecules exhibit antiangiogenesis properties and may become an alternative for further therapeutic angiogenesis

ANIMAL & CELL MODELS

NOA mice