CCL5

CCL5
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1B3A, 1EQT, 1HRJ, 1RTN, 1RTO, 1U4L, 1U4M, 1U4P, 1U4R, 2L9H, 2VXW, 5CMD, 5DNF, 5COY
Identifikatori
Aliasi	CCL5
Vanjski ID-jevi	OMIM: 187011 MGI: 98262 HomoloGene: 2244 GeneCards: CCL5
Lokacija gena (čovjek) Hrom. Hromosom 17 (čovjek)[1] Bend 17q12 Početak 35,871,491 bp[1] Kraj 35,880,793 bp[1]
Lokacija gena (miš) Hrom. Hromosom 11 (miš)[2] Bend 11 C|11 50.66 cM Početak 83,416,604 bp[2] Kraj 83,421,344 bp[2]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • CCR5 chemokine receptor binding • receptor signaling protein tyrosine kinase activator activity • chemokine activity • protein self-association • CCR4 chemokine receptor binding • phosphatidylinositol phospholipase C activity • protein kinase activity • cytokine activity • CCR1 chemokine receptor binding • phospholipase activator activity • chemokine receptor binding • protein homodimerization activity • chemokine receptor antagonist activity • GO:0001948, GO:0016582 vezivanje za proteine • chemoattractant activity • vezivanje identičnih proteina • CCR chemokine receptor binding Ćelijska komponenta • citoplazma • extracellular region • Vanćelijsko Biološki proces • leukocyte cell-cell adhesion • positive regulation of cell-cell adhesion mediated by integrin • regulation of T cell activation • positive regulation of smooth muscle cell migration • activation of phospholipase D activity • negative regulation of viral genome replication • positive regulation of ERK1 and ERK2 cascade • positive regulation of innate immune response • cellular response to interferon-gamma • positive regulation of macrophage chemotaxis • calcium ion transport • Egzocitoza • positive regulation of calcium ion transport • response to cytokine • regulation of insulin secretion • chemokine-mediated signaling pathway • positive regulation of cellular biosynthetic process • response to virus • positive regulation of monocyte chemotaxis • cellular response to fibroblast growth factor stimulus • neutrophil chemotaxis • response to tumor necrosis factor • negative regulation of T cell apoptotic process • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • negative regulation of macrophage apoptotic process • positive regulation of T cell proliferation • positive regulation of phosphorylation • inflammatory response • positive regulation of translational initiation • response to toxic substance • positive regulation of epithelial cell proliferation • positive regulation of tyrosine phosphorylation of STAT protein • GO:1904579 cellular response to organic cyclic compound • cellular calcium ion homeostasis • protein tetramerization • Hemotaksija • positive regulation of homotypic cell-cell adhesion • cellular response to interleukin-1 • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • positive regulation of viral genome replication • positive regulation of receptor signaling pathway via JAK-STAT • lipopolysaccharide-mediated signaling pathway • positive regulation of T cell migration • regulation of chronic inflammatory response • positive regulation of smooth muscle cell proliferation • neutrophil activation • protein kinase B signaling • positive regulation of cell migration • positive regulation of natural killer cell chemotaxis • cell-cell signaling • eosinophil chemotaxis • dendritic cell chemotaxis • MAPK cascade • macrophage chemotaxis • positive regulation of T cell chemotaxis • regulation of neuron death • positive regulation of phosphatidylinositol 3-kinase signaling • negative regulation of G protein-coupled receptor signaling pathway • positive regulation of T cell apoptotic process • positive regulation of cell adhesion • negative regulation of chemokine-mediated signaling pathway • monocyte chemotaxis • positive chemotaxis • positive regulation of protein tyrosine kinase activity • cellular response to tumor necrosis factor • positive regulation of activation of Janus kinase activity • regulation of signaling receptor activity • G protein-coupled receptor signaling pathway • cytokine-mediated signaling pathway • lymphocyte chemotaxis Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	6352	20304
Ensembl	ENSG00000271503 ENSG00000274233	ENSMUSG00000035042
UniProt	P13501	P30882
RefSeq (mRNK)	NM_002985 NM_001278736	NM_013653
RefSeq (bjelančevina)	NP_001265665 NP_002976	NP_038681
Lokacija (UCSC)	Chr 17: 35.87 – 35.88 Mb	Chr 11: 83.42 – 83.42 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Hemokinski
(C-C motivni)
ligand 5
(CCL5) je protein koji je kod ljudi kodiran genom CCL5.^[5] Poznat je i pod nazivom RANTES (reguliran aktivacijom, normalni T ćelija-eksprimirani i lučeni).

Dužina polipeptidnog lanca je 91 aminokiselina, a molekulska težina 9.990 Da.^[6]

Sekvenca

Simboli

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
MKVSAAALAV		ILIATALCAP		ASASPYSSDT		TPCCFAYIAR		PLPRAHIKEY
FYTSGKCSNP		AVVFVTRKNR		QVCANPEKKW		VREYINSLEM		S

Funkcija

CCL5 je 8-kDa-ltonski protein klasificiran kao hemotaksijski citokin ili hemokin. CCL5 je hemotaksičan za T-ćelije, eozinofile i bazofile i ima aktivnu ulogu u regrutovanju leukocita na upalna mjesta. Uz pomoć određenih citokina (tj. IL-2 i IFN-γ) koje oslobađaju T-ćelije , CCL5 također inducira proliferaciju i aktivaciju određenih ćelija prirodnog ubica (NK) da bi se stvorile CHAK ćelije (CC-hemokinski-aktivirane ubice).^[7] Također je supresivni faktor HIV-a koji se oslobađa iz CD8 + T ćelija.^[8] Ovaj hemokinski gen je kod ljudi lokaliziran na hromosomu 17.^[5]

RANTES je prvi put identificiran u potrazi za genima eksprimiranim kao "kasno", (3-5 dana) nakon aktivacije T-ćelija. Naknadno je utvrđeno da je to CC hemokin i eksprimiran u više od 100 ljudskih bolesti. Ekspresija RANTES-a u T-limfocitima je regulirana Kruppelovim faktorom 13 (KLF13).^{[9][10][11][12]} RANTES je, zajedno sa srodnim hemokinima MIP-1alfa i MIP-1beta, identificiran kao prirodni HIV-supresivni faktor kojeg luče aktivirane CD8 + T-ćelije i druge imunske ćelije.^[8] Nedavno je protein RANTES dizajniran za proizvodnju in vivo kod bakterija Lactobacillus, a ovo rešenje se razvija u mogući lokalni mikrobicid koji inhibira ulazak HIV-a.^[13]

Interakcije

Pokazano je da CCL5 komunicira sa CCR3,^[14][15] CCR5^{[15][16][17][18]} i CCR1.^[15][17]

CCL5 također aktivira receptor povezan sa G-proteinima GPR75.^[19]

Također pogledajte

• Hemotaksija
• Hemokin

Reference

1. ENSG00000274233 GRCh38: Ensembl release 89: ENSG00000271503, ENSG00000274233 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035042 - 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. Donlon TA, Krensky AM, Wallace MR, Collins FS, Lovett M, Clayberger C (mart 1990). "Localization of a human T-cell-specific gene, RANTES (D17S136E), to chromosome 17q11.2-q12" (PDF). Genomics. 6 (3): 548–53. doi:10.1016/0888-7543(90)90485-D. hdl:2027.42/28717. PMID 1691736.
6. "UniProt, P13501". Pristupljeno 27. 6. 2021.
7. Maghazachi AA, Al-Aoukaty A, Schall TJ (februar 1996). "CC chemokines induce the generation of killer cells from CD56+ cells". Eur. J. Immunol. 26 (2): 315–9. doi:10.1002/eji.1830260207. PMID 8617297.
8. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P (decembar 1995). "Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells". Science. 270 (5243): 1811–5. doi:10.1126/science.270.5243.1811. PMID 8525373. S2CID 84062618.
9. Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, Krensky AM (august 1988). "A human T cell-specific molecule is a member of a new gene family". J. Immunol. 141 (3): 1018–25. PMID 2456327.
10. Alan M. Krensky (1995). Biology of the Chemokine in Rantes (Molecular Biology Intelligence Unit). R G Landes Co. ISBN 978-1-57059-253-9.
11. Song A, Chen YF, Thamatrakoln K, Storm TA, Krensky AM (januar 1999). "RFLAT-1: a new zinc finger transcription factor that activates RANTES gene expression in T lymphocytes". Immunity. 10 (1): 93–103. doi:10.1016/S1074-7613(00)80010-2. PMID 10023774.
12. Song A, Nikolcheva T, Krensky AM (oktobar 2000). "Transcriptional regulation of RANTES expression in T lymphocytes". Immunol. Rev. 177: 236–45. doi:10.1034/j.1600-065X.2000.17610.x. PMID 11138780. S2CID 30184294.
13. Vangelista L, Secchi M, Liu X, Bachi A, Jia L, Xu Q, Lusso P (juli 2010). "Engineering of Lactobacillus jensenii to secrete RANTES and a CCR5 antagonist analogue as live HIV-1 blockers". Antimicrob. Agents Chemother. 54 (7): 2994–3001. doi:10.1128/AAC.01492-09. PMC 2897324. PMID 20479208. Sažetak – Science Daily.
14. Daugherty BL, Siciliano SJ, DeMartino JA, Malkowitz L, Sirotina A, Springer MS (maj 1996). "Cloning, expression, and characterization of the human eosinophil eotaxin receptor". J. Exp. Med. 183 (5): 2349–54. doi:10.1084/jem.183.5.2349. PMC 2192548. PMID 8642344.
15. Struyf S, Menten P, Lenaerts JP, Put W, D'Haese A, De Clercq E, Schols D, Proost P, Van Damme J (juli 2001). "Diverging binding capacities of natural LD78beta isoforms of macrophage inflammatory protein-1alpha to the CC chemokine receptors 1, 3 and 5 affect their anti-HIV-1 activity and chemotactic potencies for neutrophils and eosinophils". Eur. J. Immunol. 31 (7): 2170–8. doi:10.1002/1521-4141(200107)31:7<2170::AID-IMMU2170>3.0.CO;2-D. PMID 11449371.
16. Slimani H, Charnaux N, Mbemba E, Saffar L, Vassy R, Vita C, Gattegno L (oktobar 2003). "Interaction of RANTES with syndecan-1 and syndecan-4 expressed by human primary macrophages". Biochim. Biophys. Acta. 1617 (1–2): 80–8. doi:10.1016/j.bbamem.2003.09.006. PMID 14637022.
17. Proudfoot AE, Fritchley S, Borlat F, Shaw JP, Vilbois F, Zwahlen C, Trkola A, Marchant D, Clapham PR, Wells TN (april 2001). "The BBXB motif of RANTES is the principal site for heparin binding and controls receptor selectivity". J. Biol. Chem. 276 (14): 10620–6. doi:10.1074/jbc.M010867200. PMID 11116158.
18. Laplana M, Fibla J (april 2012). "Distribution of functional polymorphic variants of inflammation-related genes RANTES and CCR5 in long-lived individuals". Cytokine. 58 (1): 10–13. doi:10.1016/j.cyto.2011.12.021. PMID 22265023.
19. Ignatov A, Robert J, Gregory-Evans C, Schaller HC (novembar 2006). "RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75". Br. J. Pharmacol. 149 (5): 490–7. doi:10.1038/sj.bjp.0706909. PMC 2014681. PMID 17001303.

Dopunska literatura

• Muthumani K, Desai BM, Hwang DS, Choo AY, Laddy DJ, Thieu KP, Rao RG, Weiner DB (2004). "HIV-1 Vpr and anti-inflammatory activity". DNA Cell Biol. 23 (4): 239–47. doi:10.1089/104454904773819824. PMID 15142381.
• Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation". Cell Res. 15 (3): 143–9. doi:10.1038/sj.cr.7290279. PMID 15780175.
• Zhao RY, Bukrinsky M, Elder RT (2005). "HIV-1 viral protein R (Vpr) & host cellular responses". Indian J. Med. Res. 121 (4): 270–86. PMID 15817944.
• Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Res. 15 (11–12): 923–34. doi:10.1038/sj.cr.7290370. PMID 16354571.
• Ignatov A, Robert J, Gregory-Evans C, Schaller HC (Nov 2006). "RANTES stimulates Ca2+ mobilization and inositol trisphosphate (IP3) formation in cells transfected with G protein-coupled receptor 75". Br J Pharmacol. 149 (5): 490–7. doi:10.1038/sj.bjp.0706909. PMC 2014681. PMID 17001303.

Vanjski linkovi

• Lokacija ljudskog genoma CCL5 i stranica sa detaljima o genu CCL5 u UCSC Genome Browseru.
• P13501