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P02776 (PLF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Platelet factor 4

Short name=PF-4
Alternative name(s):
C-X-C motif chemokine 4
Iroplact
Oncostatin-A

Cleaved into the following chain:

  1. Platelet factor 4, short form
Gene names
Name:PF4
Synonyms:CXCL4, SCYB4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length101 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Released during platelet aggregation. Neutralizes the anticoagulant effect of heparin because it binds more strongly to heparin than to the chondroitin-4-sulfate chains of the carrier molecule. Chemotactic for neutrophils and monocytes. Inhibits endothelial cell proliferation, the short form is a more potent inhibitor than the longer form. Ref.11

Subunit structure

Homotetramer. Ref.13 Ref.14

Subcellular location

Secreted.

Sequence similarities

Belongs to the intercrine alpha (chemokine CxC) family.

Mass spectrometry

Molecular mass is 7765 Da from positions 32 - 101. Determined by ESI. Ref.11

Molecular mass is 6033 Da from positions 48 - 101. Determined by ESI. Short form. Ref.11

Ontologies

Keywords
   Biological processChemotaxis
   Cellular componentSecreted
   DomainSignal
   LigandHeparin-binding
   Molecular functionCytokine
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cytokine-mediated signaling pathway

Inferred from direct assay PubMed 12041672. Source: UniProtKB

immune response

Inferred from electronic annotation. Source: InterPro

leukocyte chemotaxis

Inferred from direct assay PubMed 6945600. Source: UniProtKB

negative regulation of MHC class II biosynthetic process

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

negative regulation of angiogenesis

Inferred from direct assay PubMed 1688470. Source: UniProtKB

negative regulation of cytolysis

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

negative regulation of extrinsic apoptotic signaling pathway in absence of ligand

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

negative regulation of megakaryocyte differentiation

Inferred from direct assay PubMed 2140694. Source: UniProtKB

platelet activation

Inferred from direct assay PubMed 11685038. Source: UniProtKB

platelet degranulation

Traceable author statement. Source: Reactome

positive regulation of cAMP metabolic process

Inferred from direct assay PubMed 12782716. Source: UniProtKB

positive regulation of cAMP-mediated signaling

Inferred from direct assay PubMed 12782716. Source: UniProtKB

positive regulation of gene expression

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

positive regulation of macrophage derived foam cell differentiation

Inferred from direct assay PubMed 17244792. Source: BHF-UCL

positive regulation of macrophage differentiation

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12782716. Source: UniProtKB

positive regulation of tumor necrosis factor production

Inferred from direct assay PubMed 10666185. Source: BHF-UCL

regulation of cell proliferation

Inferred from direct assay PubMed 12782716. Source: UniProtKB

   Cellular_componentextracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

platelet alpha granule lumen

Traceable author statement. Source: Reactome

   Molecular_functionCXCR3 chemokine receptor binding

Inferred from direct assay PubMed 12782716. Source: UniProtKB

chemokine activity

Traceable author statement PubMed 12466273. Source: UniProtKB

heparin binding

Inferred from direct assay PubMed 9531587. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
Chain32 – 10170Platelet factor 4
PRO_0000005068
Chain48 – 10154Platelet factor 4, short form
PRO_0000351217

Regions

Region92 – 987Heparin-binding

Amino acid modifications

Disulfide bond41 ↔ 67 Ref.10 Ref.13 Ref.14
Disulfide bond43 ↔ 83 Ref.10 Ref.13 Ref.14

Experimental info

Sequence conflict781N → D AA sequence Ref.8
Sequence conflict781N → D AA sequence Ref.9

Secondary structure

.................. 101
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P02776 [UniParc].

Last modified July 1, 1989. Version 2.
Checksum: E96C2EFE9B944D85

FASTA10110,845
        10         20         30         40         50         60 
MSSAAGFCAS RPGLLFLGLL LLPLVVAFAS AEAEEDGDLQ CLCVKTTSQV RPRHITSLEV 

        70         80         90        100 
IKAGPHCPTA QLIATLKNGR KICLDLQAPL YKKIIKKLLE S 

« Hide

References

« Hide 'large scale' references
[1]"Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line."
Poncz M., Surrey S., Larocco P., Weiss M.J., Rappaport E.F., Conway T.M., Schwartz E.
Blood 69:219-223(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structural and functional comparison of the genes for human platelet factor 4 and PF4alt."
Eisman R., Surrey S., Ramachandran B., Schwartz E., Poncz M.
Blood 76:336-344(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus."
Zhang C., Thornton M.A., Kowalska M.A., Sachis B.S., Feldman M., Poncz M., McKenzie S.E., Reilly M.P.
Blood 98:610-617(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]"Isolation, crystallization, and primary amino acid sequence of human platelet factor 4."
Hermodson M., Schmer G., Kurachi K.
J. Biol. Chem. 252:6276-6279(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-101.
[8]"Amino acid sequence of human platelet factor 4."
Deuel T.F., Keim P.S., Farmer M., Heinrikson R.L.
Proc. Natl. Acad. Sci. U.S.A. 74:2256-2258(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-101.
[9]"Primary structure of human platelet factor 4."
Walz D.A., Wu V.Y., de Lamo R., Dene H., McCoy L.E.
Thromb. Res. 11:893-898(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-101.
[10]"Complete covalent structure of human platelet factor 4."
Morgan F.J., Begg G.S., Chesterman C.N.
Thromb. Haemost. 42:1652-1660(1980) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-101.
[11]"A potent inhibitor of endothelial cell proliferation is generated by proteolytic cleavage of the chemokine platelet factor 4."
Gupta S.K., Hassel T., Singh J.P.
Proc. Natl. Acad. Sci. U.S.A. 92:7799-7803(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 32-101, N-TERMINAL CLEAVAGE, FUNCTION, MASS SPECTROMETRY.
Tissue: Leukocyte.
[12]"Alternative C-terminal helix orientation alters chemokine function: Structure of the Anti-angiogenic Chemokine, CXCL4L1."
Kuo J.H., Chen Y.P., Liu J.S., Dubrac A., Quemener C., Prats H., Bikfalvi A., Wu W.G., Sue S.C.
J. Biol. Chem. 288:13522-13533(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: HEPARIN-BINDING REGION.
[13]"Crystal structure of recombinant human platelet factor 4."
Zhang X., Chen L., Bancroft D.P., Lai C.K., Maione T.E.
Biochemistry 33:8361-8366(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), SUBUNIT, DISULFIDE BONDS.
[14]"NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer."
Mayo K.H., Roongta V., Ilyina E., Milius R., Barker S., Quinlan C., La Rosa G., Daly T.J.
Biochemistry 34:11399-11409(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 43-101, SUBUNIT, DISULFIDE BONDS.
+Additional computationally mapped references.

Web resources

Wikipedia

CXCL4 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M25897 mRNA. Translation: AAA60066.1.
AF349466 Genomic DNA. Translation: AAK29643.1.
CR407677 mRNA. Translation: CAG28605.1.
AC097709 Genomic DNA. Translation: AAY41003.1.
BC093965 mRNA. Translation: AAH93965.1.
BC112093 mRNA. Translation: AAI12094.1.
PIRPFHU4. A60161.
RefSeqNP_002610.1. NM_002619.3.
UniGeneHs.81564.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DN3NMR-A87-101[»]
1F9QX-ray2.00A/B/C/D32-101[»]
1F9RX-ray2.00A/B/C/D32-101[»]
1F9SX-ray2.38A/B/C/D32-101[»]
1PFMNMR-A/B/C/D43-101[»]
1PFNNMR-A/B/C/D43-101[»]
1RHPX-ray2.40A/B/C/D32-101[»]
ProteinModelPortalP02776.
SMRP02776. Positions 36-101.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111219. 7 interactions.
IntActP02776. 2 interactions.
STRING9606.ENSP00000296029.

Chemistry

DrugBankDB00055. Drotrecogin alfa.

Polymorphism databases

DMDM130304.

2D gel databases

OGPP02776.

Proteomic databases

PaxDbP02776.
PeptideAtlasP02776.
PRIDEP02776.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296029; ENSP00000296029; ENSG00000163737.
GeneID5196.
KEGGhsa:5196.
UCSCuc003hhi.3. human.

Organism-specific databases

CTD5196.
GeneCardsGC04M074836.
HGNCHGNC:8861. PF4.
HPACAB026008.
HPA052485.
MIM173460. gene.
neXtProtNX_P02776.
PharmGKBPA33203.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG40449.
HOGENOMHOG000220915.
HOVERGENHBG107789.
InParanoidP02776.
KOK05407.
OMACAVPQLI.
OrthoDBEOG7B5WZS.
PhylomeDBP02776.
TreeFamTF333433.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

BgeeP02776.
CleanExHS_PF4.
GenevestigatorP02776.

Family and domain databases

InterProIPR001089. Chemokine_CXC.
IPR018048. Chemokine_CXC_CS.
IPR001811. Chemokine_IL8-like_dom.
IPR027222. PF4.
[Graphical view]
PANTHERPTHR10179. PTHR10179. 1 hit.
PTHR10179:SF10. PTHR10179:SF10. 1 hit.
PfamPF00048. IL8. 1 hit.
[Graphical view]
PRINTSPR00437. SMALLCYTKCXC.
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
PROSITEPS00471. SMALL_CYTOKINES_CXC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP02776.
GeneWikiPlatelet_factor_4.
GenomeRNAi5196.
NextBio20098.
PMAP-CutDBP02776.
PROP02776.
SOURCESearch...

Entry information

Entry namePLF4_HUMAN
AccessionPrimary (citable) accession number: P02776
Secondary accession number(s): Q53X61, Q9UC64, Q9UC65
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 1, 1989
Last modified: April 16, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM