PF4 platelet factor 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PF4provided by HGNC
Official Full Name: platelet factor 4provided by HGNC
Primary source: HGNC:HGNC:8861
See related: Ensembl:ENSG00000163737 MIM:173460; AllianceGenome:HGNC:8861
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PF-4; CXCL4; SCYB4
Summary: This gene encodes a member of the CXC chemokine family. This chemokine is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell type and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. The protein also exhibits antimicrobial activity against Plasmodium falciparum. [provided by RefSeq, Oct 2014]
Expression: Biased expression in bone marrow (RPKM 14.3), spleen (RPKM 2.7) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 4q13.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (73980811..73982124, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (77324459..77325772, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (74846528..74847841, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies.
Title: The Binding of the SARS-CoV-2 Spike Protein to Platelet Factor 4: A Proposed Mechanism for the Generation of Pathogenic Antibodies.
Hyperactivation of beta-catenin signal in hepatocellular carcinoma recruits myeloid-derived suppressor cells through PF4-CXCR3 axis.
Title: Hyperactivation of β-catenin signal in hepatocellular carcinoma recruits myeloid-derived suppressor cells through PF4-CXCR3 axis.
Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.
Title: Platelet factor 4 limits neutrophil extracellular trap- and cell-free DNA-induced thrombogenicity and endothelial injury.
Platelet factor 4(PF4) and its multiple roles in diseases.
Title: Platelet factor 4(PF4) and its multiple roles in diseases.
Platelet factor 4 induces bone loss by inhibiting the integrin alpha5-FAK-ERK pathway.
Title: Platelet factor 4 induces bone loss by inhibiting the integrin α5-FAK-ERK pathway.
PF4 activates the c-Mpl-Jak2 pathway in platelets.
Title: PF4 activates the c-Mpl-Jak2 pathway in platelets.
New insights into the binding of PF4 to long heparin oligosaccharides in ultralarge complexes using mass spectrometry.
Title: New insights into the binding of PF4 to long heparin oligosaccharides in ultralarge complexes using mass spectrometry.
Platelet factor 4 (PF4) induces cluster of differentiation 40 (CD40) expression in human aortic endothelial cells (HAECs) through the SIRT1/NF-kappaB/p65 signaling pathway.
Title: Platelet factor 4 (PF4) induces cluster of differentiation 40 (CD40) expression in human aortic endothelial cells (HAECs) through the SIRT1/NF-κB/p65 signaling pathway.
Platelet-instructed SPP1[+] macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner.
Title: Platelet-instructed SPP1(+) macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner.
Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity.
Title: Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity.

Submit: New GeneRIF Correction See all GeneRIFs (183)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
In single-round infection assays, HIV-1 NL4-3 psuedotyped with Env proteins from subtypes B and C entry is enhanced by high concentrations of tetrameric PF4 (CXCR4) in MAGI-R5 cells	PubMed
HIV-1 CH077 virus entry is enhanced by high concentrations of PF4 (CXCR4) in MAGI-R5, SupT1-R5, Jurkat-R5, and primary CD4+ T cells	PubMed
In single-round infection assays, HIV-1 NL4-3 pseudotyped with Env proteins from subtypes B and C entry is enhanced by high concentrations of tetrameric PF4 (CXCR4) in MAGI-R5 cells	PubMed
HIV-1 CH077 virus entry is inhibited by low concentrations of PF4 (CXCR4) in MAGI-R5, SupT1-R5, Jurkat-R5, and primary CD4+ T cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 JRFL Env (gp120) binds specifically to polystyrene-immobilized PF4 (CXCL4) and CCL5 (RANTES) as measured through ELISA	PubMed
	env	CXCL4 directly interacts with HIV-1 gp120 and the CXCL4-binding site is located within the gp120 outer domain (residues 350-455) proximal to the CD4-binding site	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:481307

SHGC-67990 (e-PCR)
- UniSTS:46629

SHGC-50926 (e-PCR)
- UniSTS:72804

SHGC-59547 (e-PCR)
- UniSTS:10383

NoName (e-PCR)
- UniSTS:483297

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables CXCR chemokine receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables CXCR3 chemokine receptor binding	IDA Inferred from Direct Assay more info	PubMed
enables chemokine activity	IBA Inferred from Biological aspect of Ancestor more info
enables chemokine activity	TAS Traceable Author Statement more info	PubMed
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in adenylate cyclase-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemokine-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cytokine-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to protozoan	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in killing by host of symbiont cells	IDA Inferred from Direct Assay more info	PubMed
involved_in leukocyte chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of MHC class II biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of angiogenesis	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of megakaryocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in neutrophil chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in platelet activation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage derived foam cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of tumor necrosis factor production	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	NAS Non-traceable Author Statement more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: platelet factor 4

Names: C-X-C motif chemokine 4; chemokine (C-X-C motif) ligand 4; iroplact; oncostatin-A

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032897.1 RefSeqGene

Range

5098..6314

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_636

mRNA and Protein(s)

NM_001363352.1 → NP_001350281.1 platelet factor 4 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice site which results in the use of an alternate start codon, compared to variant 1. It encodes a longer protein (isoform 2) with a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AC097709

Conserved Domains (1) summary

cd00273
Location:47 → 109

Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...
NM_002619.4 → NP_002610.1 platelet factor 4 isoform 1 precursor

See identical proteins and their annotated locations for NP_002610.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript and encodes the shorter isoform (1).

Source sequence(s)

AC097709, GD143506, M25897

Consensus CDS

CCDS3562.1

UniProtKB/Swiss-Prot

P02776, Q53X61, Q9UC64, Q9UC65

Related

ENSP00000296029.3, ENST00000296029.4

Conserved Domains (1) summary

cd00273
Location:38 → 100

Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...