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PF4 platelet factor 4 [ Homo sapiens (human) ]

Gene ID: 5196, updated on 3-Oct-2018

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; Vega:OTTHUMG00000130009
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

Genomic context

See PF4 in Genome Data Viewer
Location:
4q13.3
Exon count:
3
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 4 NC_000004.12 (73980825..73982124, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (74846542..74847841, complement)

Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene heterogeneous nuclear ribonucleoprotein A1 pseudogene 55 Neighboring gene C-X-C motif chemokine ligand 1 pseudogene 1 Neighboring gene pro-platelet basic protein Neighboring gene C-X-C motif chemokine ligand 5

Genomic regions, transcripts, and products

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

HIV-1 interactions

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

Pathways from BioSystems

  • CXCR3-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CXCR3-mediated signaling events, organism-specific biosystem
    CXCR3-mediated signaling events
  • Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
    Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
  • Chemokine receptors bind chemokines, organism-specific biosystem (from REACTOME)
    Chemokine receptors bind chemokines, organism-specific biosystemChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of i...
  • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
    Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Chemokine signaling pathway, conserved biosystem (from KEGG)
    Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
  • Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
    Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
  • Common Pathway of Fibrin Clot Formation, organism-specific biosystem (from REACTOME)
    Common Pathway of Fibrin Clot Formation, organism-specific biosystemThe common pathway consists of the cascade of activation events leading from the formation of activated factor X to the formation of active thrombin, the cleavage of fibrinogen by thrombin, and the f...
  • Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
    Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
  • Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
    Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
  • G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
    G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
  • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
    GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
  • GPCR ligand binding, organism-specific biosystem (from REACTOME)
    GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
  • Hemostasis, organism-specific biosystem (from REACTOME)
    Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
  • Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
    Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
  • Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
    Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...
  • Platelet degranulation, organism-specific biosystem (from REACTOME)
    Platelet degranulation, organism-specific biosystemPlatelets function as exocytotic cells, secreting a plethora of effector molecules at sites of vascular injury. Platelets contain a number of distinguishable storage granules including alpha granules...
  • Response to elevated platelet cytosolic Ca2+, organism-specific biosystem (from REACTOME)
    Response to elevated platelet cytosolic Ca2+, organism-specific biosystemActivation of phospholipase C enzymes results in the generation of second messengers of the phosphatidylinositol pathway. The events resulting from this pathway are a rise in intracellular calcium an...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by GPCR, organism-specific biosystem (from REACTOME)
    Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC138298

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CXCR3 chemokine receptor binding IDA
Inferred from Direct Assay
more info
PubMed 
chemokine activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine activity TAS
Traceable Author Statement
more info
PubMed 
heparin binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
G protein-coupled receptor signaling pathway TAS
Traceable Author Statement
more info
 
adenylate cyclase-activating G protein-coupled receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
antimicrobial humoral immune response mediated by antimicrobial peptide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
antimicrobial humoral immune response mediated by antimicrobial peptide IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to lipopolysaccharide IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
chemokine-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytokine-mediated signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
defense response to protozoan IDA
Inferred from Direct Assay
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
killing by host of symbiont cells IDA
Inferred from Direct Assay
more info
PubMed 
leukocyte chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
leukocyte chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of MHC class II biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of angiogenesis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cytolysis IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of megakaryocyte differentiation IDA
Inferred from Direct Assay
more info
PubMed 
neutrophil chemotaxis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
platelet activation IDA
Inferred from Direct Assay
more info
PubMed 
platelet degranulation TAS
Traceable Author Statement
more info
 
positive regulation of cAMP-mediated signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of macrophage derived foam cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of macrophage differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of tumor necrosis factor production IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of megakaryocyte differentiation TAS
Traceable Author Statement
more info
 
regulation of signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
collagen-containing extracellular matrix HDA PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
extracellular region NAS
Non-traceable Author Statement
more info
PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
other organism cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
platelet alpha granule lumen TAS
Traceable Author Statement
more info
 
symbiont-containing vacuole membrane IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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)

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

  1. NG_032897.1 RefSeqGene

    Range
    5001..6300
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001363352.1NP_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:47109
    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 ...
  2. NM_002619.3NP_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
    Related
    ENSP00000296029.3, OTTHUMP00000160478, ENST00000296029.3, OTTHUMT00000252282
    Conserved Domains (1) summary
    cd00273
    Location:38100
    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 ...

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p12 Primary Assembly

    Range
    73980825..73982124 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005265696.4XP_005265753.1  platelet factor 4 isoform X1

    Conserved Domains (1) summary
    cd00273
    Location:47109
    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 ...
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