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).

CCL5
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1B3A, 1EQT, 1HRJ, 1RTN, 1RTO, 1U4L, 1U4M, 1U4P, 1U4R, 2L9H, 2VXW, 5CMD, 5DNF, 5COY

Identifikatori
AliasiCCL5
Vanjski ID-jeviOMIM: 187011 MGI: 98262 HomoloGene: 2244 GeneCards: CCL5
Lokacija gena (čovjek)
Hromosom 17 (čovjek)
Hrom.Hromosom 17 (čovjek)[1]
Hromosom 17 (čovjek)
Genomska lokacija za CCL5
Genomska lokacija za CCL5
Bend17q12Početak35,871,491 bp[1]
Kraj35,880,793 bp[1]
Lokacija gena (miš)
Hromosom 11 (miš)
Hrom.Hromosom 11 (miš)[2]
Hromosom 11 (miš)
Genomska lokacija za CCL5
Genomska lokacija za CCL5
Bend11 C|11 50.66 cMPočetak83,416,604 bp[2]
Kraj83,421,344 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
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_002985
NM_001278736

NM_013653

RefSeq (bjelančevina)

NP_001265665
NP_002976

NP_038681

Lokacija (UCSC)Chr 17: 35.87 – 35.88 MbChr 11: 83.42 – 83.42 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

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

Sekvenca

Simboli

1020304050
MKVSAAALAVILIATALCAPASASPYSSDTTPCCFAYIARPLPRAHIKEY
FYTSGKCSNPAVVFVTRKNRQVCANPEKKWVREYINSLEMS

Funkcija

uredi

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

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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

uredi

Reference

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  1. ^ a b c ENSG00000274233 GRCh38: Ensembl release 89: ENSG00000271503, ENSG00000274233 - Ensembl, maj 2017
  2. ^ a b c 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. ^ a b 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. ^ a b 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. SažetakScience 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. ^ a b c 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. ^ a b 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

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Vanjski linkovi

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