CCL8

CCL8
Dostupne strukture
PDB	Pretraga Human UniProta: PDBe RCSB
Spisak PDB ID kodova
	1ESR
Identifikatori
Aliasi	CCL8
Vanjski ID-jevi	OMIM: 602283 HomoloGene: 48362 GeneCards: CCL8
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	34,321,402 bp
Ontologija gena
Molekularna funkcija	• protein kinase activity; • cytokine activity; • heparin binding; • phospholipase activator activity; • CCR chemokine receptor binding; • chemokine activity; • GO:0001948, GO:0016582 vezivanje za proteine; • CCR2 chemokine receptor binding;
Ćelijska komponenta	• extracellular region; • Vanćelijsko;
Biološki proces	• G protein-coupled receptor signaling pathway; • monocyte chemotaxis; • chemokine-mediated signaling pathway; • cellular response to tumor necrosis factor; • cell-cell signaling; • response to virus; • cellular calcium ion homeostasis; • neutrophil chemotaxis; • Hemotaksija; • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity; • cellular response to interleukin-1; • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor; • positive regulation of ERK1 and ERK2 cascade; • cellular response to interferon-gamma; • lymphocyte chemotaxis; • inflammatory response; • calcium ion transport; • GO:0072468 Transdukcija signala; • Egzocitoza; • protein phosphorylation; • antimicrobial humoral immune response mediated by antimicrobial peptide; • positive regulation of leukocyte migration; • negative regulation of leukocyte proliferation; • regulation of signaling receptor activity; • Angiogeneza; • eosinophil chemotaxis;
	Izvori:Amigo / QuickGO
Ortolozi
	6355
	n/a
	ENSG00000108700
	n/a
	P80075
	n/a
	NM_005623
	n/a
	NP_005614
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek

Hemokinski (C-C motivni) ligand 8 (CCL8), znan i kao monocitni hemoatraktantni protein 2 (MCP2), je protein koji je kod ljudi kodiran genom CCL8.^[3]^[4]

CCL8 je mali citokin koji pripada porodici CC hemokina. CCL8 protein se proizvodi kao prekursor koji sadrži 109 aminokiselina, a koji se cijepa da bi se dobio zreli CCL8 koji sadrži 75 aminokiselina. Kod ljudi, gen za CCL8 ima tri egzona i nalazi se unutar velikog skupa CC hemokinskih gena na hromosomu 17 q11.2.^[4]^[5] MCP-2 je hemotaksijski i aktivira mnoge različite imunske ćelije, uključujući mastocite, eozinofile i bazofile (koje su uključene u alergijske reakcije) i monocite, T-ćelije i NK-ćelije koji su uključeni u upalni odgovor.^[6]^[7] Svoje efekte CCL8 izaziva vezanjem na nekoliko različitih receptora na ćelijskoj površini, zvanih hemokinski receptori. Ovi receptori uključuju CCR1, CCR2B, CCR3 i CCR5.^[7]^[8]

CCL8 je CC-hemokin koji koristi više ćelijskih receptora za privlačenje i aktiviranje ljudskih leukocita. CCL8 je snažni inhibitor HIV 1, zahvaljujući visokom afinitetu vezanja za receptor CCR5, jedan od glavnih koreceptora za HIV1.^[9] Pored toga, CCL8 –u pripisuje se rast metastaza u ćelijama raka dojke. Manipulacija ovom hemokinskom aktivnošću utiče na histologiju tumora, promovirajući korake metastatskih procesa.^[10] CCL8 je također uključen u privlačenje makrofaga u porođajnu deciduu.^[11]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 99 aminokiselina, a molekulska težina 11.246 Da.^[12]

10		20		30		40		50
MKVSAALLCL		LLMAATFSPQ		GLAQPDSVSI		PITCCFNVIN		RKIPIQRLES
YTRITNIQCP		KEAVIFKTKR		GKEVCADPKE		RWVRDSMKHL		DQIFQNLKP

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

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000108700 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: chemokine (C-C motif) ligand 8".
^ ^a ^b Van Coillie E, Fiten P, Nomiyama H, Sakaki Y, Miura R, Yoshie O, Van Damme J, Opdenakker G (mart 1997). "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2". Genomics. 40 (2): 323–31. doi:10.1006/geno.1996.4594. PMID 9119400.
^ Van Damme J, Proost P, Lenaerts JP, Opdenakker G (juli 1992). "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family". J. Exp. Med. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.
^ Proost P, Wuyts A, Van Damme J (januar 1996). "Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1". J. Leukoc. Biol. 59 (1): 67–74. doi:10.1002/jlb.59.1.67. PMID 8558070. S2CID 30445255.
^ ^a ^b Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM (februar 1998). "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". J. Biol. Chem. 273 (8): 4289–92. doi:10.1074/jbc.273.8.4289. PMID 9468473.
^ Ge B, Li J, Wei Z, Sun T, Song Y, Khan NU (2017). "Functional expression of CCL8 and its interaction with chemokine receptor CCR3". BMC Immunol. 18 (1): 54. doi:10.1186/s12865-017-0237-5. PMC 5745793. PMID 29281969.
^ PDB 1ESR; Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X (novembar 2000). "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors". Biochemistry. 39 (46): 14075–81. doi:10.1021/bi0009340. PMID 11087354.
^ Farmaki E, Chatzistamou I, Kaza V, Kiaris H (2016). "A CCL8 gradient drives breast cancer cell dissemination". Oncogene. 35 (49): 6309–6318. doi:10.1038/onc.2016.161. PMC 5112152. PMID 27181207.
^ Hamilton SA, Tower CL, Jones RL (2013). "Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour". PLOS ONE. 8 (2): e56946. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.
^ "UniProt, P80075". Pristupljeno 27. 6. 2021.

Vanjski linkovi

Lokacija ljudskog genoma CCL8 i stranica sa detaljima o genu CCL8 u UCSC Genome Browseru.

Dopunska literatura

Struyf S, Proost P, Vandercappellen J, et al. (2009). "Synergistic up-regulation of MCP-2/CCL8 activity is counteracted by chemokine cleavage, limiting its inflammatory and anti-tumoral effects". Eur. J. Immunol. 39 (3): 843–57. doi:10.1002/eji.200838660. PMID 19224633.
Rom S, Rom I, Passiatore G, et al. (2010). "CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells". FASEB J. 24 (7): 2292–300. doi:10.1096/fj.09-143503. PMC 2887261. PMID 20181935.
Menon R, Pearce B, Velez DR, et al. (2009). "Racial disparity in pathophysiologic pathways of preterm birth based on genetic variants". Reprod. Biol. Endocrinol. 7: 62. doi:10.1186/1477-7827-7-62. PMC 2714850. PMID 19527514.
Segat L, Brandão LA, Guimarães RL, et al. (2010). "Polymorphisms in innate immunity genes and patients response to dendritic cell-based HIV immuno-treatment". Vaccine. 28 (10): 2201–6. doi:10.1016/j.vaccine.2009.12.056. PMID 20056178.
Rajaraman P, Brenner AV, Butler MA, et al. (2009). "Common variation in genes related to innate immunity and risk of adult glioma". Cancer Epidemiol. Biomarkers Prev. 18 (5): 1651–8. doi:10.1158/1055-9965.EPI-08-1041. PMC 2771723. PMID 19423540.
Han S, Lan Q, Park AK, et al. (2010). "Polymorphisms in innate immunity genes and risk of childhood leukemia". Hum. Immunol. 71 (7): 727–30. doi:10.1016/j.humimm.2010.04.004. PMC 2967770. PMID 20438785.
Velez DR, Fortunato SJ, Thorsen P, et al. (2008). "Preterm birth in Caucasians is associated with coagulation and inflammation pathway gene variants". PLOS ONE. 3 (9): e3283. doi:10.1371/journal.pone.0003283. PMC 2553267. PMID 18818748.
Villa C, Venturelli E, Fenoglio C, et al. (2009). "CCL8/MCP-2 association analysis in patients with Alzheimer's disease and frontotemporal lobar degeneration". J. Neurol. 256 (8): 1379–81. doi:10.1007/s00415-009-5138-y. PMID 19415413. S2CID 3147096.
Siezen CL, Bont L, Hodemaekers HM, et al. (2009). "Genetic susceptibility to respiratory syncytial virus bronchiolitis in preterm children is associated with airway remodeling genes and innate immune genes". Pediatr. Infect. Dis. J. 28 (4): 333–5. doi:10.1097/INF.0b013e31818e2aa9. PMID 19258923. S2CID 25601837.
Vyshkina T, Sylvester A, Sadiq S, et al. (2008). "CCL genes in multiple sclerosis and systemic lupus erythematosus". J. Neuroimmunol. 200 (1–2): 145–52. doi:10.1016/j.jneuroim.2008.05.016. PMC 5301077. PMID 18602166.
Ruhwald M, Bodmer T, Maier C, et al. (2008). "Evaluating the potential of IP-10 and MCP-2 as biomarkers for the diagnosis of tuberculosis". Eur. Respir. J. 32 (6): 1607–15. doi:10.1183/09031936.00055508. PMID 18684849.
Skibola CF, Bracci PM, Halperin E, et al. (2008). "Polymorphisms in the estrogen receptor 1 and vitamin C and matrix metalloproteinase gene families are associated with susceptibility to lymphoma". PLOS ONE. 3 (7): e2816. doi:10.1371/journal.pone.0002816. PMC 2474696. PMID 18636124.
Ockinger J, Stridh P, Beyeen AD, et al. (2010). "Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis". Genes Immun. 11 (2): 142–54. doi:10.1038/gene.2009.82. PMID 19865101.
Xie Z, Zhang J, Wu J, et al. (2008). "Upregulation of mitochondrial uncoupling protein-2 by the AMP-activated protein kinase in endothelial cells attenuates oxidative stress in diabetes". Diabetes. 57 (12): 3222–30. doi:10.2337/db08-0610. PMC 2584127. PMID 18835932.
Rajaraman P, Brenner AV, Neta G, et al. (2010). "Risk of meningioma and common variation in genes related to innate immunity". Cancer Epidemiol. Biomarkers Prev. 19 (5): 1356–61. doi:10.1158/1055-9965.EPI-09-1151. PMC 3169167. PMID 20406964.
Velez DR, Fortunato S, Thorsen P, et al. (2009). "Spontaneous preterm birth in African Americans is associated with infection and inflammatory response gene variants". Am. J. Obstet. Gynecol. 200 (2): 209.e1–27. doi:10.1016/j.ajog.2008.08.051. PMC 4829203. PMID 19019335.
Dean RA, Cox JH, Bellac CL, et al. (2008). "Macrophage-specific metalloelastase (MMP-12) truncates and inactivates ELR+ CXC chemokines and generates CCL2, -7, -8, and -13 antagonists: potential role of the macrophage in terminating polymorphonuclear leukocyte influx". Blood. 112 (8): 3455–64. doi:10.1182/blood-2007-12-129080. PMID 18660381.
Hori T, Naishiro Y, Sohma H, et al. (2008). "CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease". Blood. 111 (8): 4403–12. doi:10.1182/blood-2007-06-097287. PMC 2288733. PMID 18256320.
Schuurhof A, Bont L, Siezen CL, et al. (2010). "Interleukin-9 polymorphism in infants with respiratory syncytial virus infection: an opposite effect in boys and girls". Pediatr. Pulmonol. 45 (6): 608–13. doi:10.1002/ppul.21229. PMID 20503287.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000108700 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-3] "Entrez Gene: chemokine (C-C motif) ligand 8".

[pmid9119400-4] Van Coillie E, Fiten P, Nomiyama H, Sakaki Y, Miura R, Yoshie O, Van Damme J, Opdenakker G (mart 1997). "The human MCP-2 gene (SCYA8): cloning, sequence analysis, tissue expression, and assignment to the CC chemokine gene contig on chromosome 17q11.2". Genomics. 40 (2): 323–31. doi:10.1006/geno.1996.4594. PMID 9119400.

[pmid1613466-5] Van Damme J, Proost P, Lenaerts JP, Opdenakker G (juli 1992). "Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family". J. Exp. Med. 176 (1): 59–65. doi:10.1084/jem.176.1.59. PMC 2119277. PMID 1613466.

[pmid8558070-6] Proost P, Wuyts A, Van Damme J (januar 1996). "Human monocyte chemotactic proteins-2 and -3: structural and functional comparison with MCP-1". J. Leukoc. Biol. 59 (1): 67–74. doi:10.1002/jlb.59.1.67. PMID 8558070. S2CID 30445255.

[Gong_1998-7] Gong W, Howard OM, Turpin JA, Grimm MC, Ueda H, Gray PW, Raport CJ, Oppenheim JJ, Wang JM (februar 1998). "Monocyte chemotactic protein-2 activates CCR5 and blocks CD4/CCR5-mediated HIV-1 entry/replication". J. Biol. Chem. 273 (8): 4289–92. doi:10.1074/jbc.273.8.4289. PMID 9468473.

[8] Ge B, Li J, Wei Z, Sun T, Song Y, Khan NU (2017). "Functional expression of CCL8 and its interaction with chemokine receptor CCR3". BMC Immunol. 18 (1): 54. doi:10.1186/s12865-017-0237-5. PMC 5745793. PMID 29281969.

[pmid11087354-9] PDB 1ESR; Blaszczyk J, Coillie EV, Proost P, Damme JV, Opdenakker G, Bujacz GD, Wang JM, Ji X (novembar 2000). "Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors". Biochemistry. 39 (46): 14075–81. doi:10.1021/bi0009340. PMID 11087354.

[10] Farmaki E, Chatzistamou I, Kaza V, Kiaris H (2016). "A CCL8 gradient drives breast cancer cell dissemination". Oncogene. 35 (49): 6309–6318. doi:10.1038/onc.2016.161. PMC 5112152. PMID 27181207.

[11] Hamilton SA, Tower CL, Jones RL (2013). "Identification of chemokines associated with the recruitment of decidual leukocytes in human labour: potential novel targets for preterm labour". PLOS ONE. 8 (2): e56946. doi:10.1371/journal.pone.0056946. PMC 3579936. PMID 23451115.

[UniProt-12] "UniProt, P80075". Pristupljeno 27. 6. 2021.

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