ID PLF4_HUMAN Reviewed; 101 AA. AC P02776; Q53X61; Q9UC64; Q9UC65; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 2. DT 02-SEP-2026, entry version 222. DE RecName: Full=Platelet factor 4; DE Short=PF-4; DE AltName: Full=C-X-C motif chemokine 4; DE AltName: Full=Iroplact; DE AltName: Full=Oncostatin-A; DE Contains: DE RecName: Full=Platelet factor 4, short form; DE AltName: Full=Endothelial cell growth inhibitor {ECO:0000303|PubMed:7644496}; DE Flags: Precursor; GN Name=PF4; Synonyms=CXCL4, SCYB4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3098319; DOI=10.1182/blood.v69.1.219.219; RA Poncz M., Surrey S., Larocco P., Weiss M.J., Rappaport E.F., Conway T.M., RA Schwartz E.; RT "Cloning and characterization of platelet factor 4 cDNA derived from a RT human erythroleukemic cell line."; RL Blood 69:219-223(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1695112; DOI=10.1182/blood.v76.2.336.336; RA Eisman R., Surrey S., Ramachandran B., Schwartz E., Poncz M.; RT "Structural and functional comparison of the genes for human platelet RT factor 4 and PF4alt."; RL Blood 76:336-344(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11468158; DOI=10.1182/blood.v98.3.610; RA Zhang C., Thornton M.A., Kowalska M.A., Sachis B.S., Feldman M., Poncz M., RA McKenzie S.E., Reilly M.P.; RT "Localization of distal regulatory domains in the megakaryocyte-specific RT platelet basic protein/platelet factor 4 gene locus."; RL Blood 98:610-617(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP PROTEIN SEQUENCE OF 32-101. RX PubMed=893407; DOI=10.1016/s0021-9258(17)39951-9; RA Hermodson M., Schmer G., Kurachi K.; RT "Isolation, crystallization, and primary amino acid sequence of human RT platelet factor 4."; RL J. Biol. Chem. 252:6276-6279(1977). RN [8] RP PROTEIN SEQUENCE OF 32-101. RX PubMed=267922; DOI=10.1073/pnas.74.6.2256; RA Deuel T.F., Keim P.S., Farmer M., Heinrikson R.L.; RT "Amino acid sequence of human platelet factor 4."; RL Proc. Natl. Acad. Sci. U.S.A. 74:2256-2258(1977). RN [9] RP PROTEIN SEQUENCE OF 32-101. RX PubMed=601757; DOI=10.1016/0049-3848(77)90117-7; RA Walz D.A., Wu V.Y., de Lamo R., Dene H., McCoy L.E.; RT "Primary structure of human platelet factor 4."; RL Thromb. Res. 11:893-898(1977). RN [10] RP PROTEIN SEQUENCE OF 32-101. RX PubMed=6445090; DOI=10.1055/s-0038-1657071; RA Morgan F.J., Begg G.S., Chesterman C.N.; RT "Complete covalent structure of human platelet factor 4."; RL Thromb. Haemost. 42:1652-1660(1980). RN [11] RP PROTEIN SEQUENCE OF 32-101, IDENTIFICATION OF PF4 SHORT FORM, FUNCTION, RP MASS SPECTROMETRY, AND SUBCELLULAR LOCATION. RC TISSUE=Leukocyte; RX PubMed=7644496; DOI=10.1073/pnas.92.17.7799; RA Gupta S.K., Hassel T., Singh J.P.; RT "A potent inhibitor of endothelial cell proliferation is generated by RT proteolytic cleavage of the chemokine platelet factor 4."; RL Proc. Natl. Acad. Sci. U.S.A. 92:7799-7803(1995). RN [12] RP FUNCTION, AND INTERACTION WITH THBD. RX PubMed=9395524; DOI=10.1074/jbc.272.50.31785; RA Dudek A.Z., Pennell C.A., Decker T.D., Young T.A., Key N.S., Slungaard A.; RT "Platelet factor 4 binds to glycanated forms of thrombomodulin and to RT protein C. A potential mechanism for enhancing generation of activated RT protein C."; RL J. Biol. Chem. 272:31785-31792(1997). RN [13] RP FUNCTION. RX PubMed=9531587; DOI=10.1182/blood.v91.8.2772.2772_2772_2780; RA Lecomte-Raclet L., Alemany M., Sequira-Le Grand A., Amiral J., Quentin G., RA Vissac A.M., Caen J.P., Han Z.C.; RT "New insights into the negative regulation of hematopoiesis by chemokine RT platelet factor 4 and related peptides."; RL Blood 91:2772-2780(1998). RN [14] RP FUNCTION, AND INTERACTION WITH CXCR3. RX PubMed=18174362; DOI=10.1189/jlb.1006645; RA Mueller A., Meiser A., McDonagh E.M., Fox J.M., Petit S.J., Xanthou G., RA Williams T.J., Pease J.E.; RT "CXCL4-induced migration of activated T lymphocytes is mediated by the RT chemokine receptor CXCR3."; RL J. Leukoc. Biol. 83:875-882(2008). RN [15] RP HEPARIN-BINDING REGION. RX PubMed=23536183; DOI=10.1074/jbc.m113.455329; RA Kuo J.H., Chen Y.P., Liu J.S., Dubrac A., Quemener C., Prats H., RA Bikfalvi A., Wu W.G., Sue S.C.; RT "Alternative C-terminal helix orientation alters chemokine function: RT Structure of the Anti-angiogenic Chemokine, CXCL4L1."; RL J. Biol. Chem. 288:13522-13533(2013). RN [16] RP FUNCTION. RX PubMed=24469069; DOI=10.1007/s10456-014-9417-6; RA Van Raemdonck K., Gouwy M., Lepers S.A., Van Damme J., Struyf S.; RT "CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular RT endothelial cells and activated lymphocytes: involvement of mitogen- RT activated protein (MAP) kinases, Src and p70S6 kinase."; RL Angiogenesis 17:631-640(2014). RN [17] RP INTERACTION WITH TNFAIP6. RX PubMed=27044744; DOI=10.1074/jbc.m116.720953; RA Dyer D.P., Salanga C.L., Johns S.C., Valdambrini E., Fuster M.M., RA Milner C.M., Day A.J., Handel T.M.; RT "The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by RT Inhibiting Chemokine/Glycosaminoglycan Interactions."; RL J. Biol. Chem. 291:12627-12640(2016). RN [18] RP FUNCTION, AND INTERACTION WITH CCR1. RX PubMed=29930254; DOI=10.1038/s41598-018-27710-9; RA Fox J.M., Kausar F., Day A., Osborne M., Hussain K., Mueller A., Lin J., RA Tsuchiya T., Kanegasaki S., Pease J.E.; RT "CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte RT migration."; RL Sci. Rep. 8:9466-9466(2018). RN [19] RP FUNCTION. RX PubMed=35701499; DOI=10.1038/s41467-022-31132-7; RA Yang C., Bachu M., Du Y., Brauner C., Yuan R., Ah Kioon M.D., Chesi G., RA Barrat F.J., Ivashkiv L.B.; RT "CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling RT and inflammatory response in human monocytes."; RL Nat. Commun. 13:3426-3426(2022). RN [20] RP FUNCTION, AND INDUCTION BY INFLAMMATORY CONDITIONS. RX PubMed=34986347; DOI=10.1016/j.celrep.2021.110189; RA Affandi A.J., Carvalheiro T., Ottria A., de Haan J.J., Brans M.A.D., RA Brandt M.M., Tieland R.G., Lopes A.P., Fernandez B.M., Bekker C.P.J., RA van der Linden M., Zimmermann M., Giovannone B., Wichers C.G.K., Garcia S., RA de Kok M., Stifano G., Xu Y.J., Kowalska M.A., Waasdorp M., Cheng C., RA Gibbs S., de Jager S.C.A., van Roon J.A.G., Radstake T.R.D.J., Marut W.; RT "CXCL4 drives fibrosis by promoting several key cellular and molecular RT processes."; RL Cell Rep. 38:110189-110189(2022). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), SUBUNIT, AND DISULFIDE BONDS. RX PubMed=8031770; DOI=10.1021/bi00193a025; RA Zhang X., Chen L., Bancroft D.P., Lai C.K., Maione T.E.; RT "Crystal structure of recombinant human platelet factor 4."; RL Biochemistry 33:8361-8366(1994). RN [22] RP STRUCTURE BY NMR OF 43-101, SUBUNIT, AND DISULFIDE BONDS. RX PubMed=7547867; DOI=10.1021/bi00036a012; RA Mayo K.H., Roongta V., Ilyina E., Milius R., Barker S., Quinlan C., RA La Rosa G., Daly T.J.; RT "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N- RT terminal chimera: a symmetric tetramer."; RL Biochemistry 34:11399-11409(1995). CC -!- FUNCTION: Chemokine released during platelet aggregation that plays a CC role in different biological processes including hematopoiesis, cell CC proliferation, differentiation, and activation (PubMed:29930254, CC PubMed:9531587). Acts via different functional receptors including CC CCR1, CXCR3A or CXCR3B (PubMed:18174362, PubMed:29930254). Upon CC interaction with CXCR3A receptor, induces activated T-lymphocytes CC migration mediated via downstream Ras/extracellular signal-regulated CC kinase (ERK) signaling (PubMed:18174362, PubMed:24469069). Neutralizes CC the anticoagulant effect of heparin by binding more strongly to heparin CC than to the chondroitin-4-sulfate chains of the carrier molecule. Plays CC a role in the inhibition of hematopoiesis and in the maintenance of CC hematopoietic stem cell (HSC) quiescence (PubMed:9531587). Chemotactic CC for neutrophils and monocytes via CCR1 (PubMed:29930254). Inhibits CC endothelial cell proliferation. In cooperation with toll-like receptor CC 8/TLR8, induces chromatin remodeling and activates inflammatory gene CC expression via the TBK1-IRF5 axis (PubMed:35701499). In addition, CC induces myofibroblast differentiation and collagen synthesis in CC different precursor cells, including endothelial cells, by stimulating CC endothelial-to-mesenchymal transition (PubMed:34986347). Interacts with CC thrombomodulin/THBD to enhance the activation of protein C and thus CC potentiates its anticoagulant activity (PubMed:9395524). CC {ECO:0000269|PubMed:18174362, ECO:0000269|PubMed:24469069, CC ECO:0000269|PubMed:29930254, ECO:0000269|PubMed:34986347, CC ECO:0000269|PubMed:35701499, ECO:0000269|PubMed:7644496, CC ECO:0000269|PubMed:9395524, ECO:0000269|PubMed:9531587}. CC -!- SUBUNIT: Homotetramer (PubMed:7547867, PubMed:8031770). Interacts with CC TNFAIP6 (via Link domain) (PubMed:27044744). Interacts with CCR1 CC (PubMed:29930254). Interacts with CXCR3 (PubMed:18174362). Interacts CC with THBD; this interaction enhances generation of activated protein C CC (PubMed:9395524). {ECO:0000269|PubMed:18174362, CC ECO:0000269|PubMed:27044744, ECO:0000269|PubMed:29930254, CC ECO:0000269|PubMed:7547867, ECO:0000269|PubMed:8031770, CC ECO:0000269|PubMed:9395524}. CC -!- INTERACTION: CC P02776; P02749: APOH; NbExp=2; IntAct=EBI-2565740, EBI-2114682; CC P02776; P51671: CCL11; NbExp=2; IntAct=EBI-2565740, EBI-727357; CC P02776; Q99616: CCL13; NbExp=2; IntAct=EBI-2565740, EBI-725342; CC P02776; Q92583: CCL17; NbExp=2; IntAct=EBI-2565740, EBI-16640146; CC P02776; P13500: CCL2; NbExp=2; IntAct=EBI-2565740, EBI-1034732; CC P02776; P78556: CCL20; NbExp=2; IntAct=EBI-2565740, EBI-3913209; CC P02776; O00585: CCL21; NbExp=2; IntAct=EBI-2565740, EBI-953695; CC P02776; O15444: CCL25; NbExp=3; IntAct=EBI-2565740, EBI-7783341; CC P02776; Q9Y258: CCL26; NbExp=3; IntAct=EBI-2565740, EBI-7783416; CC P02776; Q9NRJ3: CCL28; NbExp=3; IntAct=EBI-2565740, EBI-7783254; CC P02776; P13501: CCL5; NbExp=6; IntAct=EBI-2565740, EBI-2848366; CC P02776; PRO_0000005175 [P13501]: CCL5; NbExp=3; IntAct=EBI-2565740, EBI-11712923; CC P02776; P02778: CXCL10; NbExp=2; IntAct=EBI-2565740, EBI-7815386; CC P02776; O14625: CXCL11; NbExp=2; IntAct=EBI-2565740, EBI-2871971; CC P02776; P48061: CXCL12; NbExp=4; IntAct=EBI-2565740, EBI-3913254; CC P02776; O95715: CXCL14; NbExp=3; IntAct=EBI-2565740, EBI-2798068; CC P02776; Q6UXB2: CXCL17; NbExp=2; IntAct=EBI-2565740, EBI-16804198; CC P02776; P19875: CXCL2; NbExp=3; IntAct=EBI-2565740, EBI-2114901; CC P02776; P80162: CXCL6; NbExp=2; IntAct=EBI-2565740, EBI-9214033; CC P02776; P10145: CXCL8; NbExp=2; IntAct=EBI-2565740, EBI-3917999; CC P02776; Q07325: CXCL9; NbExp=3; IntAct=EBI-2565740, EBI-3911467; CC P02776; P47992: XCL1; NbExp=2; IntAct=EBI-2565740, EBI-10209901; CC PRO_0000005068; PRO_0000002059 [P02749]: APOH; NbExp=4; IntAct=EBI-11809981, EBI-11809989; CC PRO_0000005068; P0DTC2: S; Xeno; NbExp=3; IntAct=EBI-11809981, EBI-25474821; CC PRO_0000351217; P13501: CCL5; NbExp=2; IntAct=EBI-20561364, EBI-2848366; CC PRO_0000351217; PRO_0000005175 [P13501]: CCL5; NbExp=2; IntAct=EBI-20561364, EBI-11712923; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7644496}. CC -!- INDUCTION: By inflammatory conditions. {ECO:0000269|PubMed:34986347}. CC -!- MASS SPECTROMETRY: [Platelet factor 4]: Mass=7765; Method=Electrospray; CC Evidence={ECO:0000269|PubMed:7644496}; CC -!- MASS SPECTROMETRY: [Platelet factor 4, short form]: Mass=6033; CC Method=Electrospray; Note=Short form.; CC Evidence={ECO:0000269|PubMed:7644496}; CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=CXCL4 entry; CC URL="https://en.wikipedia.org/wiki/CXCL4"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M25897; AAA60066.1; -; mRNA. DR EMBL; AF349466; AAK29643.1; -; Genomic_DNA. DR EMBL; CR407677; CAG28605.1; -; mRNA. DR EMBL; AC097709; AAY41003.1; -; Genomic_DNA. DR EMBL; BC093965; AAH93965.1; -; mRNA. DR EMBL; BC112093; AAI12094.1; -; mRNA. DR CCDS; CCDS3562.1; -. DR PIR; A60161; PFHU4. DR RefSeq; NP_002610.1; NM_002619.4. DR PDB; 1DN3; NMR; -; A=87-101. DR PDB; 1F9Q; X-ray; 2.00 A; A/B/C/D=32-101. DR PDB; 1F9R; X-ray; 2.00 A; A/B/C/D=32-101. DR PDB; 1F9S; X-ray; 2.38 A; A/B/C/D=32-101. DR PDB; 1PFM; NMR; -; A/B/C/D=38-101. DR PDB; 1PFN; NMR; -; A/B/C/D=38-101. DR PDB; 1RHP; X-ray; 2.40 A; A/B/C/D=32-101. DR PDB; 4R9W; X-ray; 2.50 A; A/B=32-101. DR PDB; 4R9Y; X-ray; 4.11 A; A/B/C/D=32-101. DR PDB; 4RAU; X-ray; 3.74 A; C/F/I/L/O/R/U/X=32-101. DR AlphaFoldDB; P02776; -. DR SMR; P02776; -. DR BioGRID; 111219; 30. DR DIP; DIP-56941N; -. DR FunCoup; P02776; 644. DR IntAct; P02776; 30. DR MINT; P02776; -. DR NDEx; IQUERY-CP-PF4; 6 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000296029; -. DR BindingDB; P02776; -. DR ChEMBL; CHEMBL3286075; -. DR DrugBank; DB00055; Drotrecogin alfa. DR DrugBank; DB01109; Heparin. DR PhosphoSitePlus; P02776; -. DR BioMuta; PF4; -. DR DMDM; 130304; -. DR OGP; P02776; -. DR MassIVE; P02776; -. DR PaxDb; 9606-ENSP00000296029; -. DR PeptideAtlas; P02776; -. DR ProteomicsDB; 51593; -. DR TopDownProteomics; P02776; -. DR ABCD; P02776; 2 sequenced antibodies. DR Antibodypedia; 24586; 547 antibodies from 38 providers. DR DNASU; 5196; -. DR Ensembl; ENST00000296029.4; ENSP00000296029.3; ENSG00000163737.5. DR GeneID; 5196; -. DR KEGG; hsa:5196; -. DR MANE-Select; ENST00000296029.4; ENSP00000296029.3; NM_002619.4; NP_002610.1. DR UCSC; uc003hhi.4; human. DR AGR; HGNC:8861; -. DR ClinPGx; PA33203; -. DR CTD; 5196; -. DR DisGeNET; 5196; -. DR GeneCards; PF4; -. DR HGNC; HGNC:8861; PF4. DR HPA; ENSG00000163737; Group enriched (bone marrow, lymphoid tissue). DR MIM; 173460; gene. DR OpenTargets; ENSG00000163737; -. DR VEuPathDB; HostDB:ENSG00000163737; -. DR eggNOG; ENOG502TF57; Eukaryota. DR GeneTree; ENSGT00940000163666; -. DR HOGENOM; CLU_143902_1_2_1; -. DR InParanoid; P02776; -. DR OMA; CAVPQLI; -. DR OrthoDB; 9937393at2759; -. DR PAN-GO; P02776; 7 GO annotations based on evolutionary models. DR PhylomeDB; P02776; -. DR PathwayCommons; P02776; -. DR Reactome; R-HSA-114608; Platelet degranulation. DR Reactome; R-HSA-202733; Cell surface interactions at the vascular wall. DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function. DR Reactome; R-HSA-9769739; Regulation of clotting cascade. DR SignaLink; P02776; -. DR Agora; ENSG00000163737; -. DR BioGRID-ORCS; 5196; 20 hits in 1096 CRISPR screens. DR EvolutionaryTrace; P02776; -. DR GeneWiki; Platelet_factor_4; -. DR GenomeRNAi; 5196; -. DR Pharos; P02776; Tbio. DR PRO; PR:P02776; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P02776; protein. DR Bgee; ENSG00000163737; Expressed in monocyte and 121 other cell types or tissues. DR ExpressionAtlas; P02776; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; HDA:BHF-UCL. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome. DR GO; GO:0008009; F:chemokine activity; IDA:UniProt. DR GO; GO:0045236; F:CXCR chemokine receptor binding; IBA:GO_Central. DR GO; GO:0048248; F:CXCR3 chemokine receptor binding; IDA:UniProtKB. DR GO; GO:0008201; F:heparin binding; IDA:UniProtKB. DR GO; GO:0048018; F:receptor ligand activity; IDA:UniProt. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0042832; P:defense response to protozoan; IDA:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0030595; P:leukocyte chemotaxis; IDA:UniProtKB. DR GO; GO:0002548; P:monocyte chemotaxis; IDA:UniProt. DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB. DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:UniProt. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IDA:BHF-UCL. DR GO; GO:0045653; P:negative regulation of megakaryocyte differentiation; IDA:UniProtKB. DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IDA:BHF-UCL. DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central. DR GO; GO:0030168; P:platelet activation; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IDA:BHF-UCL. DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL. DR GO; GO:0042127; P:regulation of cell population proliferation; IDA:UniProtKB. DR CDD; cd00273; Chemokine_CXC; 1. DR FunFam; 2.40.50.40:FF:000004; C-X-C motif chemokine; 1. DR Gene3D; 2.40.50.40; -; 1. DR InterPro; IPR039809; Chemokine_b/g/d. DR InterPro; IPR001089; Chemokine_CXC. DR InterPro; IPR018048; Chemokine_CXC_CS. DR InterPro; IPR001811; Chemokine_IL8-like_dom. DR InterPro; IPR033899; CXC_Chemokine_domain. DR InterPro; IPR036048; Interleukin_8-like_sf. DR PANTHER; PTHR12015:SF211; PLATELET FACTOR 4; 1. DR PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1. DR Pfam; PF00048; IL8; 1. DR PRINTS; PR00436; INTERLEUKIN8. DR PRINTS; PR00437; SMALLCYTKCXC. DR SMART; SM00199; SCY; 1. DR SUPFAM; SSF54117; Interleukin 8-like chemokines; 1. DR PROSITE; PS00471; SMALL_CYTOKINES_CXC; 1. DR PDBsum; 1DN3; -. DR PDBsum; 1F9Q; -. DR PDBsum; 1F9R; -. DR PDBsum; 1F9S; -. DR PDBsum; 1PFM; -. DR PDBsum; 1PFN; -. DR PDBsum; 1RHP; -. DR PDBsum; 4R9W; -. DR PDBsum; 4R9Y; -. DR PDBsum; 4RAU; -. PE 1: Evidence at protein level; KW 3D-structure; Chemotaxis; Cytokine; Direct protein sequencing; KW Disulfide bond; Heparin-binding; Phosphoprotein; Proteomics identification; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..31 FT /evidence="ECO:0000269|PubMed:267922, FT ECO:0000269|PubMed:601757, ECO:0000269|PubMed:6445090, FT ECO:0000269|PubMed:7644496, ECO:0000269|PubMed:893407" FT CHAIN 32..101 FT /note="Platelet factor 4" FT /id="PRO_0000005068" FT CHAIN 48..101 FT /note="Platelet factor 4, short form" FT /evidence="ECO:0000269|PubMed:7644496" FT /id="PRO_0000351217" FT BINDING 92..98 FT /ligand="heparin" FT /ligand_id="ChEBI:CHEBI:28304" FT MOD_RES 57 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P06765" FT DISULFID 41..67 FT /evidence="ECO:0000269|PubMed:6445090" FT DISULFID 43..83 FT /evidence="ECO:0000269|PubMed:6445090" FT CONFLICT 78 FT /note="N -> D (in Ref. 8; AA sequence and 9; AA sequence)" FT /evidence="ECO:0000305" FT STRAND 38..40 FT /evidence="ECO:0007829|PDB:1PFN" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:1F9Q" FT HELIX 52..54 FT /evidence="ECO:0007829|PDB:1F9Q" FT STRAND 55..61 FT /evidence="ECO:0007829|PDB:1F9Q" FT STRAND 64..66 FT /evidence="ECO:0007829|PDB:1F9S" FT STRAND 67..69 FT /evidence="ECO:0007829|PDB:1F9Q" FT STRAND 71..76 FT /evidence="ECO:0007829|PDB:1F9Q" FT STRAND 77..79 FT /evidence="ECO:0007829|PDB:1PFM" FT STRAND 81..83 FT /evidence="ECO:0007829|PDB:1F9Q" FT STRAND 86..88 FT /evidence="ECO:0007829|PDB:1F9Q" FT HELIX 90..99 FT /evidence="ECO:0007829|PDB:1F9Q" SQ SEQUENCE 101 AA; 10845 MW; E96C2EFE9B944D85 CRC64; MSSAAGFCAS RPGLLFLGLL LLPLVVAFAS AEAEEDGDLQ CLCVKTTSQV RPRHITSLEV IKAGPHCPTA QLIATLKNGR KICLDLQAPL YKKIIKKLLE S //