PF4

Protein identityUniProt · HPA

UniProt accession

P02776

Gene

PF4

Ensembl

ENSG00000163737

Chromosome

4

Canonical length

101 aa

Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Plasma proteins, Predicted secreted proteins

Secretome location

Secreted to blood

Quaternary structure

Homotetramer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

101 residues, UniProt reviewed canonical sequence.

>P02776|PF4
     1  MSSAAGFCAS RPGLLFLGLL LLPLVVAFAS AEAEEDGDLQ CLCVKTTSQV RPRHITSLEV
    61  IKAGPHCPTA QLIATLKNGR KICLDLQAPL YKKIIKKLLE S

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PF4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.49

Highest tissue expression

28 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PF4.

Disease | AutoantibodyPubMed

Conditions in which antibodies against PF4 are reported. Each links to that disease's full target list.

• Thrombocytopenia 34
• COVID-19 23
• Thrombosis 21
• Purpura, Thrombocytopenic, Idiopathic 16
• Purpura, Thrombotic Thrombocytopenic 3

Showing 5 of 6 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for PF4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.73

gnomAD pLI

0.04

gnomAD missense Z

0.26

DepMap mean gene effect

-0.24

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• antimicrobial humoral immune response mediated by antimicrobial peptide
• cellular response to lipopolysaccharide
• cytokine-mediated signaling pathway
• defense response to protozoan
• inflammatory response
• killing by host of symbiont cells
• leukocyte chemotaxis
• monocyte chemotaxis
• negative regulation of angiogenesis
• negative regulation of blood coagulation
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• negative regulation of megakaryocyte differentiation
• negative regulation of MHC class II biosynthetic process
• neutrophil chemotaxis
• platelet activation
• positive regulation of gene expression
• positive regulation of macrophage derived foam cell differentiation
• positive regulation of macrophage differentiation
• positive regulation of transcription by RNA polymerase II
• positive regulation of tumor necrosis factor production
• regulation of cell population proliferation

Molecular functions

• chemokine activity
• CXCR chemokine receptor binding
• CXCR3 chemokine receptor binding
• heparin binding
• receptor ligand activity

Cellular components

• cytoplasm
• extracellular matrix
• extracellular region
• extracellular space
• platelet alpha granule lumen

Protein domainsUniProt · Pfam · InterPro

• CXC chemokine
• Chemokine interleukin-8-like domain
• CXC chemokine, conserved site
• CXC Chemokine domain
• Chemokine interleukin-8-like superfamily
• Chemokine beta/gamma/delta
• Small cytokines (intecrine/chemokine), interleukin-8 like

KeywordsUniProt

• Chemotaxis
• Cytokine
• Disulfide bond
• Heparin-binding
• Phosphoprotein
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of PF4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CCR1
• CXCR3
• THBD
• TNFAIP6
• CXCL12