P02776 (PLF4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	101 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Subcellular location	Secreted.
Post-translational modification	Binds non-covalently to a proteoglycan molecule.
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 process	Chemotaxis
Cellular component	Secreted
Domain	Signal
Ligand	Heparin-binding
Molecular function	Cytokine
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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 apoptotic process Inferred from direct assay PubMed 10666185. Source: BHF-UCL negative regulation of cytolysis 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 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 tumor necrosis factor production Inferred from direct assay PubMed 10666185. Source: BHF-UCL
Cellular_component	extracellular 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_function	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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Ref.7 Ref.8 Ref.9 Ref.10 Ref.11

Chain

32 – 101

70

Platelet factor 4

PRO_0000005068

Chain

48 – 101

54

Platelet factor 4, short form

PRO_0000351217

Amino acid modifications

Disulfide bond

41 ↔ 67

Ref.10

Disulfide bond

43 ↔ 83

Ref.10

Experimental info

Sequence conflict

78

1

N → D AA sequence Ref.8

Sequence conflict

78

1

N → D AA sequence Ref.9

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

101

Helix Strand Turn

Details...

Beta strand

42 – 44

3

Helix

52 – 54

3

Beta strand

55 – 61

7

Beta strand

64 – 66

3

Beta strand

67 – 69

3

Beta strand

71 – 76

6

Beta strand

77 – 79

3

Beta strand

81 – 83

3

Beta strand

86 – 88

3

Helix

90 – 99

10

Sequences

	Sequence		Length	Mass (Da)
	P02776 [UniParc]. Last modified July 1, 1989. Version 2. Checksum: E96C2EFE9B944D85	FASTA	101	10,845
	10 20 30 40 50 60 MSSAAGFCAS RPGLLFLGLL LLPLVVAFAS AEAEEDGDLQ CLCVKTTSQV RPRHITSLEV 70 80 90 100 IKAGPHCPTA QLIATLKNGR KICLDLQAPL YKKIIKKLLE S

References

	« Hide 'large scale' referencesShow '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. , 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]	"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).
+	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.

IPI

IPI00022446.

PIR

PFHU4. A60161.

RefSeq

NP_002610.1. NM_002619.3.

UniGene

Hs.81564.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1DN3	NMR	-	A	87-101	[»]
1F9Q	X-ray	2.00	A/B/C/D	32-101	[»]
1F9R	X-ray	2.00	A/B/C/D	32-101	[»]
1F9S	X-ray	2.38	A/B/C/D	32-101	[»]
1PFM	NMR	-	A/B/C/D	43-101	[»]
1PFN	NMR	-	A/B/C/D	43-101	[»]
1RHP	X-ray	2.40	A/B/C/D	32-101	[»]

ProteinModelPortal

P02776.

ModBase

Search...

Protein-protein interaction databases

IntAct

P02776. 1 interaction.

STRING

9606.ENSP00000296029.

Polymorphism databases

DMDM

130304.

2D gel databases

OGP

P02776.

Proteomic databases

PaxDb

P02776.

PeptideAtlas

P02776.

PRIDE

P02776.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296029; ENSP00000296029; ENSG00000163737.

GeneID

5196.

KEGG

hsa:5196.

UCSC

uc003hhi.2. human.

Organism-specific databases

CTD

5196.

GeneCards

GC04M074836.

HGNC

HGNC:8861. PF4.

HPA

CAB026008.
HPA052485.

MIM

173460. gene.

neXtProt

NX_P02776.

PharmGKB

PA33203.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG40449.

HOGENOM

HOG000220915.

HOVERGEN

HBG107789.

InParanoid

P02776.

KO

K05407.

OMA

CAVPQLI.

OrthoDB

EOG49PB13.

PhylomeDB

P02776.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

Bgee

P02776.

CleanEx

HS_PF4.

Genevestigator

P02776.

GermOnline

ENSG00000163737. Homo sapiens.

Family and domain databases

InterPro

IPR001089. Chemokine_CXC.
IPR018048. Chemokine_CXC_CS.
IPR001811. Chemokine_IL8-like_dom.
IPR027222. PF4.
[Graphical view]

PANTHER

PTHR10179. PTHR10179. 1 hit.
PTHR10179:SF10. PTHR10179:SF10. 1 hit.

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

PRINTS

PR00437. SMALLCYTKCXC.

SMART

SM00199. SCY. 1 hit.
[Graphical view]

SUPFAM

SSF54117. Chemokine_IL8. 1 hit.

PROSITE

PS00471. SMALL_CYTOKINES_CXC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00055. Drotrecogin alfa.

EvolutionaryTrace

P02776.

GenomeRNAi

5196.

NextBio

20098.

PMAP-CutDB

P02776.

SOURCE

Search...

Entry information

Entry name

PLF4_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 134 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.