CXCL4

Trombocitni faktor 4 (PF4) jest mali hemokin koji je kod ljudi kodiran genom CXCL4 sa hromosoma 4. Pripada porodici hemokina CXC koja je poznata i kao hemokinski ligand 4 (C-X-C motiv). Ovaj se hemokin oslobađa iz alfa-granule aktiviranih trombocita tokom njihove agregacije i podstiče koagulaciju krvi ublažavanjem učinaka molekula sličnih heparinu . Zbog ovih dejstava, predviđa se da ima ulogu u zarastanju rana i upalama.^[5] Obično se nalazi u kompleksu s proteoglikanom.

PF4
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1RHP, 1DN3, 1F9Q, 1F9R, 1F9S, 1PFM, 1PFN, 4R9W, 4R9Y, 4RAU
Identifikatori
Aliasi	PF4
Vanjski ID-jevi	OMIM: 173460 MGI: 1888711 HomoloGene: 87791 GeneCards: PF4
Lokacija gena (čovjek) Hrom. Hromosom 4 (čovjek)[1] Bend 4q13.3 Početak 73,980,811 bp[1] Kraj 73,982,027 bp[1]
Lokacija gena (miš) Hrom. Hromosom 5 (miš)[2] Bend 5|5 E1 Početak 90,920,294 bp[2] Kraj 90,921,242 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • cytokine activity • heparin binding • CXCR3 chemokine receptor binding • chemokine activity • GO:0001948, GO:0016582 vezivanje za proteine Ćelijska komponenta • extracellular region • platelet alpha granule lumen • Vanćelijsko • citoplazma • collagen-containing extracellular matrix Biološki proces • cytokine-mediated signaling pathway • chemokine-mediated signaling pathway • positive regulation of macrophage differentiation • platelet degranulation • negative regulation of megakaryocyte differentiation • positive regulation of cAMP-mediated signaling • negative regulation of MHC class II biosynthetic process • leukocyte chemotaxis • Hemotaksija • response to lipopolysaccharide • positive regulation of macrophage derived foam cell differentiation • GO:1901313 positive regulation of gene expression • regulation of cell population proliferation • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • positive regulation of tumor necrosis factor production • negative regulation of angiogenesis • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • inflammatory response • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • negative regulation of cytolysis • platelet activation • defense response • positive regulation of neutrophil chemotaxis • antimicrobial humoral immune response mediated by antimicrobial peptide • regulation of megakaryocyte differentiation • regulation of signaling receptor activity • G protein-coupled receptor signaling pathway • adenylate cyclase-activating G protein-coupled receptor signaling pathway • neutrophil chemotaxis • cellular response to lipopolysaccharide Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	5196	56744
Ensembl	ENSG00000163737	ENSMUSG00000029373
UniProt	P02776	Q9Z126
RefSeq (mRNK)	NM_002619 NM_001363352	NM_019932
RefSeq (bjelančevina)	NP_002610 NP_001350281	NP_064316
Lokacija (UCSC)	Chr 4: 73.98 – 73.98 Mb	Chr 5: 90.92 – 90.92 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je101 aminokiselina, а molekulska težina 10.845 Da.^[6].

• C: Cistein
• D: Asparaginska kiselina
• E: Glutaminska kiselina
• F: Fenilalanin
• G: Glicin
• H: Histidin
• I: Izoleucin
• K: Lizin
• L: Leucin
• M: Metionin
• N: Asparagin
• P: Prolin
• Q: Glutamin
• R: Arginin
• S: Serin
• T: Treonin
• V: Valin
• W: Triptofan
• Y: Tirozin

10		20		30		40		50
MSSAAGFCAS		RPGLLFLGLL		LLPLVVAFAS		AEAEEDGDLQ		CLCVKTTSQV
RPRHITSLEV		IKAGPHCPTA		QLIATLKNGR		KICLDLQAPL		YKKIIKKLLE
S

Funkcija

Trombocitni faktor-4 je protein od 70 aminokiselina koji se oslobađa iz alfa granula aktiviranih trombocita i veže se s visokim afinitetom za heparin. Čini se da je njegova glavna fiziološka uloga neutraliziranje molekula sličnih heparinu na endotelnoj površini krvnih dugova, čime se inhibira lokalna antitrombinska aktivnost i podstiče koagulacija. Kao snažan hemoatraktant za neutrofile i fibroblaste, PF4 vjerovatno ima ulogu u upali i popravci rana.^[5][7]

PF4 je ima hemotaksijsku aktuvnost aa neutrofil , fibroblast e i monocit, te stupa u interakciju s prerađenim varijantama transkripta receptora hemokina CXCR3, poznatim kao CXCR3-B .^[8]

Klinički značaj

Kompleks heparin: PF4 je antigen u heparin induciranoj trombocitopeniji, idiosinkratskoj autoimunskoj reakciji na primjenu antikoagulansa heparina.^[9] PF4 autoantitijela također su pronađeni kod pacijenata sa trombozom i karakteristikama koje liče na HIT, ali bez prethodne primjene heparina.^[10] Antitijela protiv PF4 implicirana su u slučajevima tromboze i trombocitopenije nakon vakcinacije Oxford–AstraZeneca ili Janssen COVID-19 vakcinama.^[11][12] Ovaj fenomen nazvan je embolija i imunotrombozna trombocitopenija izazvana vakcinom (VITT).^[13]

Povećava se kod pacijenata sa sistemskom sklerozom koji također imaju i intersticijsku plućnu bolest.^[14]

Faktor ljudskih trombocita 4 ubija malarijske parazite unutar eritrocita, selektivnom razlaganjem njihove probavne vakuole.^[15]

Također pogledajte

• Faktor aktivacije trombocita
• Trombocitni faktor rasta

Reference

1. GRCh38: Ensembl release 89: ENSG00000163737 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000029373 - Ensembl, maj 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Eisman R, Surrey S, Ramachandran B, Schwartz E, Poncz M (juli 1990). "Structural and functional comparison of the genes for human platelet factor 4 and PF4alt". Blood. 76 (2): 336–44. doi:10.1182/blood.V76.2.336.336. PMID 1695112.
6. "UniProt, P02776" (jezik: engleski). Pristupljeno 23. 10. 2021.
7. "Entrez Gene: PF4 platelet factor 4 (chemokine (C-X-C motif) ligand 4)".
8. Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, et al. (juni 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". The Journal of Experimental Medicine. 197 (11): 1537–49. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
9. Warkentin TE (mart 2007). "Drug-induced immune-mediated thrombocytopenia--from purpura to thrombosis". The New England Journal of Medicine. 356 (9): 891–3. doi:10.1056/NEJMp068309. PMID 17329695.
10. Warkentin TE, Makris M, Jay RM, Kelton JG (juli 2008). "A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia". The American Journal of Medicine. 121 (7): 632–6. doi:10.1016/j.amjmed.2008.03.012. PMID 18589060.
11. Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. (april 2021). "Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination". The New England Journal of Medicine. 384 (22): 2124–2130. doi:10.1056/NEJMoa2104882. PMC 8112568 Provjerite vrijednost parametra |pmc= (pomoć). PMID 33835768.
12. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S (april 2021). "Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination". The New England Journal of Medicine. 384 (22): 2092–2101. doi:10.1056/NEJMoa2104840. PMC 8095372. PMID 33835769.
13. Arepally GM, Ortel TL (juni 2021). "Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT): What We Know and Don't Know". Blood. doi:10.1182/blood.2021012152. PMC 8172307 Provjerite vrijednost parametra |pmc= (pomoć). PMID 34061166 Provjerite vrijednost parametra |pmid= (pomoć).
14. Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, et al. (decembar 2016). "Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease". Arthritis Research & Therapy. 18 (1): 305. doi:10.1186/s13075-016-1203-y. PMC 5203703. PMID 28038680.
15. Love MS, Millholland MG, Mishra S, Kulkarni S, Freeman KB, Pan W, et al. (decembar 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. PMC 3638032. PMID 23245326.

Dopunska literstura

• Bikfalvi A, Gimenez-Gallego G (februar 2004). "The control of angiogenesis and tumor invasion by platelet factor-4 and platelet factor-4-derived molecules". Seminars in Thrombosis and Hemostasis. 30 (1): 137–44. doi:10.1055/s-2004-822978. PMID 15034805.
• Maurer AM, Zhou B, Han ZC (decembar 2006). "Roles of platelet factor 4 in hematopoiesis and angiogenesis". Growth Factors. 24 (4): 242–52. doi:10.1080/08977190600988225. PMID 17381065. S2CID 36468865.
• Deuel TF, Keim PS, Farmer M, Heinrikson RL (juni 1977). "Amino acid sequence of human platelet factor 4". Proceedings of the National Academy of Sciences of the United States of America. 74 (6): 2256–8. Bibcode:1977PNAS...74.2256D. doi:10.1073/pnas.74.6.2256. PMC 432148. PMID 267922.
• Walz DA, Wu VY, de Lamo R, Dene H, McCoy LE (decembar 1977). "Primary structure of human platelet factor 4". Thrombosis Research. 11 (6): 893–8. doi:10.1016/0049-3848(77)90117-7. PMID 601757.
• Nath N, Lowery CT, Niewiarowski S (april 1975). "Antigenic and antiheparin properties of human platelet factor 4 (PF4)". Blood. 45 (4): 537–50. doi:10.1182/blood.V45.4.537.537. PMID 803847.
• Hermodson M, Schmer G, Kurachi K (septembar 1977). "Isolation, crystallization, and primary amino acid sequence of human platelet factor 4". The Journal of Biological Chemistry. 252 (18): 6276–9. doi:10.1016/S0021-9258(17)39951-9. PMID 893407.
• Maione TE, Gray GS, Petro J, Hunt AJ, Donner AL, Bauer SI, et al. (januar 1990). "Inhibition of angiogenesis by recombinant human platelet factor-4 and related peptides". Science. 247 (4938): 77–9. Bibcode:1990Sci...247...77M. doi:10.1126/science.1688470. PMID 1688470.
• Han ZC, Bellucci S, Tenza D, Caen JP (april 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". British Journal of Haematology. 74 (4): 395–401. doi:10.1111/j.1365-2141.1990.tb06325.x. PMID 2140694. S2CID 24529258.
• Poncz M, Surrey S, LaRocco P, Weiss MJ, Rappaport EF, Conway TM, Schwartz E (januar 1987). "Cloning and characterization of platelet factor 4 cDNA derived from a human erythroleukemic cell line". Blood. 69 (1): 219–23. doi:10.1182/blood.V69.1.219.219. PMID 3098319.
• Griffin CA, Emanuel BS, LaRocco P, Schwartz E, Poncz M (1987). "Human platelet factor 4 gene is mapped to 4q12----q21". Cytogenetics and Cell Genetics. 45 (2): 67–9. doi:10.1159/000132431. PMID 3622011.
• Senior RM, Griffin GL, Huang JS, Walz DA, Deuel TF (februar 1983). "Chemotactic activity of platelet alpha granule proteins for fibroblasts". The Journal of Cell Biology. 96 (2): 382–5. doi:10.1083/jcb.96.2.382. PMC 2112304. PMID 6187750.
• Morgan FJ, Begg GS, Chesterman CN (februar 1980). "Complete covalent structure of human platelet factor 4". Thrombosis and Haemostasis. 42 (5): 1652–60. PMID 6445090.
• Deuel TF, Senior RM, Chang D, Griffin GL, Heinrikson RL, Kaiser ET (juli 1981). "Platelet factor 4 is chemotactic for neutrophils and monocytes". Proceedings of the National Academy of Sciences of the United States of America. 78 (7): 4584–7. Bibcode:1981PNAS...78.4584D. doi:10.1073/pnas.78.7.4584. PMC 319837. PMID 6945600.
• Brown KJ, Parish CR (novembar 1994). "Histidine-rich glycoprotein and platelet factor 4 mask heparan sulfate proteoglycans recognized by acidic and basic fibroblast growth factor". Biochemistry. 33 (46): 13918–27. doi:10.1021/bi00250a047. PMID 7524669.
• Mayo KH, Roongta V, Ilyina E, Milius R, Barker S, Quinlan C, et al. (septembar 1995). "NMR solution structure of the 32-kDa platelet factor 4 ELR-motif N-terminal chimera: a symmetric tetramer". Biochemistry. 34 (36): 11399–409. doi:10.1021/bi00036a012. PMID 7547867.
• Barker S, Mayo KH (januar 1995). "Quarternary structure amplification of protein folding differences observed in 'native' platelet factor-4". FEBS Letters. 357 (3): 301–4. doi:10.1016/0014-5793(94)01384-D. PMID 7835432. S2CID 12222261.
• Zhang X, Chen L, Bancroft DP, Lai CK, Maione TE (juli 1994). "Crystal structure of recombinant human platelet factor 4". Biochemistry. 33 (27): 8361–6. doi:10.1021/bi00193a025. PMID 8031770.
• Horne MK (april 1993). "The effect of secreted heparin-binding proteins on heparin binding to platelets". Thrombosis Research. 70 (1): 91–8. doi:10.1016/0049-3848(93)90226-E. PMID 8511754.
• Kolset SO, Mann DM, Uhlin-Hansen L, Winberg JO, Ruoslahti E (april 1996). "Serglycin-binding proteins in activated macrophages and platelets". Journal of Leukocyte Biology. 59 (4): 545–54. doi:10.1002/jlb.59.4.545. PMID 8613703. S2CID 23125881.

Vanjski linkovi

• Platelet factor 4 na US National Library of Medicine Medical Subject Headings (MeSH)

Šablon:Proteoglikani

Ovaj članak uključuje tekst iz Nacionalne medicinske biblioteke Sjedinjenih Država, koji je u javnom vlasništvu.