WordNet
- be a contributing factor; "make things factor into a companys profitability"
- any of the numbers (or symbols) that form a product when multiplied together
- an independent variable in statistics
- anything that contributes causally to a result; "a number of factors determined the outcome"
- consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
- resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
- an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
- a concept whose truth can be proved; "scientific hypotheses are not facts"
- a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
- a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
- tiny bits of protoplasm found in vertebrate blood; essential for blood clotting (同)blood_platelet, thrombocyte
PrepTutorEJDIC
- (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
- 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/28 12:50:21」(JST)
[Wiki en表示]
"PF4" redirects here. For SpaceShipTwo PF04, see 2014 Virgin Galactic crash. For USN Tacoma-class patrol frigate, see USS Sausalito (PF-4). For Philippine Navy frigate, see BRP Rajah Lakandula (PF-4). For JMSDF frigate, see JDS Momi (PF-4). For 1997 PF4, see 14967 Madrid. For 1999 PF4, see 38245 Marcospontes. For PF4 receptor, see PF4 receptor.
| Platelet factor 4 |
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PDB rendering based on 1f9q.
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| Available structures |
| PDB |
Ortholog search: PDBe, RCSB |
| List of PDB id codes |
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1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 1RHP
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| Identifiers |
| Symbols |
PF4 ; CXCL4; PF-4; SCYB4 |
| External IDs |
OMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4 Gene |
| Gene ontology |
| Molecular function |
• chemokine activity
• heparin binding
• CXCR3 chemokine receptor binding
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| Cellular component |
• extracellular region
• extracellular space
• platelet alpha granule lumen
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| Biological process |
• platelet degranulation
• positive regulation of leukocyte chemotaxis
• inflammatory response
• immune response
• G-protein coupled receptor signaling pathway
• blood coagulation
• positive regulation of gene expression
• positive regulation of macrophage derived foam cell differentiation
• negative regulation of angiogenesis
• cytokine-mediated signaling pathway
• platelet activation
• leukocyte chemotaxis
• positive regulation of cAMP metabolic process
• response to lipopolysaccharide
• positive regulation of tumor necrosis factor production
• regulation of cell proliferation
• positive regulation of cAMP-mediated signaling
• negative regulation of MHC class II biosynthetic process
• positive regulation of macrophage differentiation
• negative regulation of megakaryocyte differentiation
• negative regulation of cytolysis
• positive regulation of transcription from RNA polymerase II promoter
• chemokine-mediated signaling pathway
• negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
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| Sources: Amigo / QuickGO |
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| RNA expression pattern |
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| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
| Entrez |
5196 |
56744 |
| Ensembl |
ENSG00000163737 |
ENSMUSG00000029373 |
| UniProt |
P02776 |
Q9Z126 |
| RefSeq (mRNA) |
NM_002619 |
NM_019932 |
| RefSeq (protein) |
NP_002610 |
NP_064316 |
| Location (UCSC) |
Chr 4:
73.98 – 73.98 Mb |
Chr 5:
90.77 – 90.77 Mb |
| PubMed search |
[1] |
[2] |
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Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.[1] It is usually found in a complex with proteoglycan.
Contents
- 1 Genomics
- 2 Function
- 3 Clinical significance
- 4 References
- 5 Further reading
- 6 See also
- 7 External links
Genomics
The gene for human PF4 is located on human chromosome 4.[2]
Function
Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.[1][3]
PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3B.[4]
Clinical significance
The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia, an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.[5] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[6]
The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[7]
References
- ^ a b Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (July 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood 76 (2): 336–44. PMID 1695112.
- ^ O'Donovan N, Galvin M, Morgan J (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenet Cell Genet 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098.
- ^ "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".
- ^ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". J Exp Med 197 (11): 1537–1549. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
- ^ Warkentin TE (March 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". N. Engl. J. Med. 356 (9): 891–893. doi:10.1056/NEJMp068309. PMID 17329695.
- ^ Warkentin TE, Makris M, Jay RM, Kelton JG (July 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". Am. J. Med. 121 (7): 632–636. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.
- ^ Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, Kavash RW, Costanzo MJ, Jo H, Daly TM, Williams DR, Kowalska MA, Bergman LW, Poncz M, Degrado WF, Sinnis P, Scott RW, Greenbaum DC (December 2012). "Platelet Factor 4 Activity against P. falciparum and Its Translation to Nonpeptidic Mimics as Antimalarials". Cell Host Microbe 12 (6): 815–23. doi:10.1016/j.chom.2012.10.017. PMID 23245326.
Further reading
- Bikfalvi A, Gimenez-Gallego G (2004). "The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules". Semin. Thromb. Hemost. 30 (1): 137–144. doi:10.1055/s-2004-822978. PMID 15034805.
- Maurer AM, Zhou B, Han ZC (2007). "Roles of platelet factor 4 in hematopoiesis and angiogenesis". Growth Factors 24 (4): 242–252. doi:10.1080/08977190600988225. PMID 17381065.
- Deuel TF, Keim PS, Farmer M, Heinrikson RL (1977). "Amino acid sequence of human platelet factor 4". Proc. Natl. Acad. Sci. U.S.A. 74 (6): 2256–2258. doi:10.1073/pnas.74.6.2256. PMC 432148. PMID 267922.
- Walz DA, Wu VY, de Lamo R et al. (1978). "Primary structure of human platelet factor 4". Thromb. Res. 11 (6): 893–898. doi:10.1016/0049-3848(77)90117-7. PMID 601757.
- Nath N, Lowery CT, Niewiarowski S (1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4)". Blood 45 (4): 537–50. PMID 803847.
- Hermodson M, Schmer G, Kurachi K (1977). "Isolation, crystallization, and primary amino acid sequence of human platelet factor 4". J. Biol. Chem. 252 (18): 6276–9. PMID 893407.
- Maione TE, Gray GS, Petro J et al. (1990). "Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides". Science 247 (4938): 77–79. doi:10.1126/science.1688470. PMID 1688470.
- Han ZC, Bellucci S, Tenza D, Caen JP (1990). "Negative regulation of human megakaryocytopoiesis by human platelet factor 4 and beta thromboglobulin: comparative analysis in bone marrow cultures from normal individuals and patients with essential thrombocythaemia and immune thrombocytopenic purpura". Br. J. Haematol. 74 (4): 395–401. doi:10.1111/j.1365-2141.1990.tb06325.x. PMID 2140694.
- Poncz M, Surrey S, LaRocco P et al. (1987). "Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line". Blood 69 (1): 219–23. PMID 3098319.
- Griffin CA, Emanuel BS, LaRocco P et al. (1987). "Human platelet factor 4 gene is mapped to 4q12----q21". Cytogenet. Cell Genet. 45 (2): 67–69. doi:10.1159/000132431. PMID 3622011.
- Senior RM, Griffin GL, Huang JS et al. (1983). "Chemotactic activity of platelet alpha granule proteins for fibroblasts". J. Cell Biol. 96 (2): 382–385. doi:10.1083/jcb.96.2.382. PMC 2112304. PMID 6187750.
- Morgan FJ, Begg GS, Chesterman CN (1980). "Complete covalent structure of human platelet factor 4". Thromb. Haemost. 42 (5): 1652–60. PMID 6445090.
- Deuel TF, Senior RM, Chang D et al. (1981). "Platelet factor 4 is chemotactic for neutrophils and monocytes". Proc. Natl. Acad. Sci. U.S.A. 78 (7): 4584–4587. doi:10.1073/pnas.78.7.4584. PMC 319837. PMID 6945600.
- Brown KJ, Parish CR (1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor". Biochemistry 33 (46): 13918–13927. doi:10.1021/bi00250a047. PMID 7524669.
- Mayo KH, Roongta V, Ilyina E et al. (1995). "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer". Biochemistry 34 (36): 11399–11409. doi:10.1021/bi00036a012. PMID 7547867.
- Barker S, Mayo KH (1995). "Quarternary [sic] structure amplification of protein folding differences observed in 'native' platelet factor-4". FEBS Lett. 357 (3): 301–304. doi:10.1016/0014-5793(94)01384-D. PMID 7835432.
- Zhang X, Chen L, Bancroft DP et al. (1994). "Crystal structure of recombinant human platelet factor 4". Biochemistry 33 (27): 8361–8366. doi:10.1021/bi00193a025. PMID 8031770.
- Horne MK (1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets". Thromb. Res. 70 (1): 91–98. doi:10.1016/0049-3848(93)90226-E. PMID 8511754.
- Kolset SO, Mann DM, Uhlin-Hansen L et al. (1996). "Serglycin-binding proteins in activated macrophages and platelets". J. Leukoc. Biol. 59 (4): 545–54. PMID 8613703.
See also
- Platelet-activating factor
- Platelet-derived growth factor
External links
- Platelet factor 4 at the US National Library of Medicine Medical Subject Headings (MeSH)
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PDB gallery
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1f9q: CRYSTAL STRUCTURE OF PLATELET FACTOR 4
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1f9r: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 1
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1f9s: CRYSTAL STRUCTURE OF PLATELET FACTOR 4 MUTANT 2
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1pfm: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 1-15 OF A 27-MODEL SET.
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1pfn: PF4-M2 CHIMERIC MUTANT WITH THE FIRST 10 N-TERMINAL RESIDUES OF R-PF4 REPLACED BY THE N-TERMINAL RESIDUES OF THE IL8 SEQUENCE. MODELS 16-27 OF A 27-MODEL SET.
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1rhp: CRYSTAL STRUCTURE OF RECOMBINANT HUMAN PLATELET FACTOR 4
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Cell signaling: cytokines
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| By family |
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By function/
cell |
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Index of signal transduction
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| Description |
- Intercellular
- neuropeptides
- growth factors
- cytokines
- hormones
- Cell surface receptors
- ligand-gated
- enzyme-linked
- G protein-coupled
- immunoglobulin superfamily
- integrins
- neuropeptide
- growth factor
- cytokine
- Intracellular
- adaptor proteins
- GTP-binding
- MAP kinase
- Calcium signaling
- Lipid signaling
- Pathways
- hedgehog
- Wnt
- TGF beta
- MAPK ERK
- notch
- JAK-STAT
- apoptosis
- hippo
- TLR
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Protein, glycoconjugate: glycoproteins and glycopeptides
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| Mucoproteins |
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Mucin
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- CD43
- CD164
- MUC1
- MUC2
- MUC3A
- MUC3B
- MUC4
- MUC5AC
- MUC5B
- MUC6
- MUC7
- MUC8
- MUC12
- MUC13
- MUC15
- MUC16
- MUC17
- MUC19
- MUC20
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Other
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- Haptoglobin
- Intrinsic factor
- Orosomucoid
- Peptidoglycan
- Phytohaemagglutinin
- Ovomucin
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| Proteoglycans |
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CS/DS
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- Decorin
- Biglycan
- Versican
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HS/CS
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CS
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- Chondroitin sulfate proteoglycans: Aggrecan
- Neurocan
- Brevican
- CD44
- CSPG4
- CSPG5
- Platelet factor 4
- Structural maintenance of chromosomes 3
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KS
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- Fibromodulin
- Lumican
- Keratocan
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HS
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| Other |
- Activin and inhibin
- ADAM
- Alpha 1-antichymotrypsin
- Apolipoprotein H
- CD70
- Asialoglycoprotein
- Avidin
- B-cell activating factor
- 4-1BB ligand
- Cholesterylester transfer protein
- Clusterin
- Colony-stimulating factor
- Hemopexin
- Lactoferrin
- Membrane glycoproteins
- Myelin protein zero
- Osteonectin
- Protein C
- Protein S
- Serum amyloid P component
- Sialoglycoprotein
- CD43
- Glycophorin
- Glycophorin C
- Thrombopoietin
- Thyroglobulin
- Thyroxine-binding proteins
- Transcortin
- Tumor necrosis factor alpha
- Uteroglobin
- Vitronectin
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Index of inborn errors of metabolism
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| Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
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| Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
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| Treatment |
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Index of biochemical families
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| Carbohydrates |
- Alcohols
- Glycoproteins
- Glycosides
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| Lipids |
- Eicosanoids
- Fatty acids
- Glycerides
- Phospholipids
- Sphingolipids
- Steroids
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| Nucleic acids |
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| Proteins |
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| Other |
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Measurement of soluble C-type lectin-like receptor 2 in human plasma.
- Kazama F1, Nakamura J2, Osada M1, Inoue O3, Oosawa M2, Tamura S1,4, Tsukiji N1, Aida K5, Kawaguchi A5, Takizawa S5, Kaneshige M5, Tanaka S5, Suzuki-Inoue K1, Ozaki Y1.
- Platelets.Platelets.2015 Dec;26(8):711-719. Epub 2015 Apr 9.
- Detection of platelet activation in vivo is useful to identify patients at risk of thrombotic diseases. Platelet factor 4 (PF4) and β-thromboglobulin (β-TG) are used for this purpose; however, they are easily released upon the minimal platelet activation that occurs during sampling. Soluble forms
- PMID 25856065
- Megakaryocytic emperipolesis and platelet function abnormalities in five patients with gray platelet syndrome.
- Larocca LM1, Heller PG2, Podda G3, Pujol-Moix N4, Glembotsky AC2, Pecci A5, Alberelli MA6, Balduini CL5, Landolfi R6, Cattaneo M3, De Candia E6.
- Platelets.Platelets.2015 Dec;26(8):751-757. Epub 2015 Mar 25.
- The gray platelet syndrome (GPS) is a rare congenital platelet disorder characterized by mild to moderate bleeding diathesis, macrothrombocytopenia and lack of azurophilic α-granules in platelets. Some platelet and megakaryocyte (MK) abnormalities have been described, but confirmative studies of th
- PMID 25806575
- Outcome of patients with positive heparin-platelet factor-4 antibodies: A retrospective multi-institutional observational study.
- Tapan U1, Bolla S, Daglilar ES, Chang S, Kozyreva O.
- Platelets.Platelets.2015 Nov;26(7):661-4. doi: 10.3109/09537104.2014.977243. Epub 2014 Nov 10.
- Studies show increased mortality with positive heparin-platelet factor-4 (H-PF4) antibodies, especially in hemodialysis patients. We aimed to compare mortality and thrombosis in hospitalized patients with positive, equivocal and negative H-PF4 antibody results. Information was collected on these pat
- PMID 25383658
Japanese Journal
- 血小板の血栓形成におけるvon Willebrand因子と糖蛋白Ibαの相互作用の生化学的役割
- Ju Lining,Zhu Cheng
- International review of thrombosis 9(3), 138-147, 2014-09
- NAID 40020218009
- イマチニブによる血管周皮細胞を標的としたリンパ腫の治療 (特集 血管生物学の進歩と血液内科)
Related Links
- fac·tor (făk′tər) n. 1. One that actively contributes to an accomplishment, result, or process: "Surprise is the greatest factor in war" (Tom Clancy). ... The platelet factor 4 assays, ELISA based, are also very sensitive and somewhat ...
- Factor An event, circumstance, influence, or element that plays a part in bringing about a result. A factor in a case contributes to its causation or outcome. ... The platelet factor 4 assays, ELISA based, are also very sensitive and ...
- factor /fac·tor/ (fak´ter) an agent or element that contributes to the production of a result. accelerator factor coagulation f. V. angiogenesis factor a substance that causes the growth of new blood vessels, found in tissues with high ...
Related Pictures
★リンクテーブル★
[★]
- 英
- platelet (Z), blood platelet (Z), PLT
- 同
- 栓球 thrombocyte
- 関
- 血小板血栓。血小板数 platelet count PLC
- GOO. 1468(血小板凝集 platelet aggregation)
- 半減期:1週間(異常値の出るメカニズム第2版)。4日 (SP.505)。
- 寿命：10日
- 体積：5-10 fl
- 直径：2-5μm。
- 無核。
基準値
- 15万 - 40万 /μl (2007前期解剖学授業プリント, SP.505)
- 15万 - 35万 /μl (2007前期生理学授業プリント, PT.233)
新生児
- 出典不明
産生組織
- トロンボポエチンにより巨核球の細胞質がちぎれて血流に放出される (SP.505)
貯蔵組織
組織学
- P-セレクチンを膜上に持つ
- フィブリノーゲン、フィブロネクチン、第V因子、第VIII因子、platelet factor 4、PDGF、TGF-α (BPT.89)
- ADP、ATP、Ca2+、ヒスタミン、セロトニン、エピネフリン (BPT.89)
機能 (SAN.236-237)
1.一次止血
- TXA2,セロトニンは血管収縮作用
- ADP, TXA2,セロトニンは血小板凝集
- 血小板のGpIIb/GpIIIa複合体がフィブリノゲンと結合し編み目を形成
2.血液凝固の促進
3.毛細血管機能の維持
- 毛細血管内皮細胞に融合し血管内皮を補強している → 血小板減少により点状出血を来すことになる。
膜タンパク
血小板減少による症状
- 5-10万 ：症状なし-やや止血しにくい程度
- 2-3万 ：下肢に点状出血 (→皮下出血)
- 1万以下 ：粘膜出血→臓器出血の危険あり
検査
- 抗凝固剤としてEDTAを用いた場合、EDTA依存性偽血小板減少をきたすことがある。
臨床関連
数の異常
機能の異常
[★]
- 英
- platelet factor 4, PF4
- 関
- 血小板
-PF4
[★]
- 関
- platelet factor 4
[★]
- 関
- actual、actually、in fact、in practice、indeed、practically
[★]
- 関
- element、elementary、factorial、parameter