CXCL10

CXCL10
Dostupne strukture PDB Pretraga ortologa: PDBe RCSB Spisak PDB ID kodova 1O80, 1LV9, 1O7Y, 1O7Z
Identifikatori
Aliasi	CXCL10
Vanjski ID-jevi	OMIM: 147310 MGI: 1352450 HomoloGene: 1203 GeneCards: CXCL10
Lokacija gena (čovjek) Hrom. Hromosom 4 (čovjek)[1] Bend 4q21.1 Početak 76,021,118 bp[1] Kraj 76,023,497 bp[1]
Lokacija gena (miš) Hrom. Hromosom 5 (miš)[2] Bend 5 E2|5 46.57 cM Početak 92,494,497 bp[2] Kraj 92,496,748 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 • cAMP-dependent protein kinase regulator activity • signaling receptor binding • chemoattractant activity Ćelijska komponenta • extracellular region • external side of plasma membrane • Vanćelijsko • intracellular anatomical structure Biološki proces • regulation of endothelial tube morphogenesis • negative regulation of myoblast differentiation • cellular response to heat • response to vitamin D • positive regulation of cell migration • T cell chemotaxis • chemokine-mediated signaling pathway • cell-cell signaling • response to virus • muscle organ development • positive regulation of monocyte chemotaxis • positive regulation of release of sequestered calcium ion into cytosol • endothelial cell activation • positive regulation of cAMP-mediated signaling • regulation of T cell chemotaxis • Krvotok • Hemotaksija • positive regulation of leukocyte chemotaxis • cell surface receptor signaling pathway • response to lipopolysaccharide • negative regulation of myoblast fusion • defense response to virus • regulation of cell population proliferation • GO:0046730, GO:0046737, GO:0046738, GO:0046736 Imuni odgovor • positive regulation of cell population proliferation • response to auditory stimulus • negative regulation of angiogenesis • response to cold • cellular response to lipopolysaccharide • response to gamma radiation • positive regulation of T cell migration • GO:0072468 Transdukcija signala • GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II • regulation of protein kinase activity • defense response • inflammatory response • antimicrobial humoral immune response mediated by antimicrobial peptide • regulation of signaling receptor activity • G protein-coupled receptor signaling pathway • cytokine-mediated signaling pathway • adenylate cyclase-activating G protein-coupled receptor signaling pathway • response to bacterium • neutrophil chemotaxis • leukocyte chemotaxis • positive chemotaxis • regulation of apoptotic process Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	3627	15945
Ensembl	ENSG00000169245	ENSMUSG00000034855
UniProt	P02778	P17515
RefSeq (mRNK)	NM_001565	NM_021274
RefSeq (bjelančevina)	NP_001556	NP_067249
Lokacija (UCSC)	Chr 4: 76.02 – 76.02 Mb	Chr 5: 92.49 – 92.5 Mb
PubMed pretraga	[3]	[4]
Wikipodaci
Pogledaj/uredi – čovjek Pogledaj/uredi – miš

Hemokinski ligand 10 (C-X-C motv) (CXCL10), znan i kao interferonom gama inducirani protein 10 (IP-10) ili maloinducibilni citokin B10 jest citokinski protein od 8,7 kDa, koji je kod ljudi kodiran genom CXCL10 sa hromosoma 4.^[5][6] C-X-C motiv hemokin 10 je mali citokin u porodici hemokina CXC.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 98 aminokiselina, а molekulska težina 10.881 Da.^[7]

• 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
MNQTAILICC		LIFLTLSGIQ		GVPLSRTVRC		TCISISNQPV		NPRSLEKLEI
IPASQFCPRV		EIIATMKKKG		EKRCLNPESK		AIKNLLKAVS		KERSKRSP

Struktura

Trodimenzijska kristalna struktura ovog hemokina određena je pod tri različita uslova do rezolucije do 1,92Å.^[8] Pristupni kodovi Proteinske banke podataka za strukture CXCL10 su 1lv9, 1o7y i 1o80.

Funkcija

CXCL10 se izlučuje u nekoliko tipova ćelija, kao odgovor na IFN-γ. Ovi tipovi ćelija uključuju monocite, endotelne ćelije i fibroblaste.^[5] Pripisuje mu se nekoliko uloga, kao što je hemoatrakcija za monocite / makrofage, T-ćelije, NK-ćelije i dendritske ćelije, promocija adhezije T-ćelija na endotelne ćelije, antitumorske aktivnosti i inhibicije formiranja kolonija koštane srži i angiogeneze.^[9][10] Ovaj hemokin izaziva svoje efekte vezivanjem za hemokinske receprtore CXCR3 na površini ćelije.^[11]

Biomarkeri

CXCL9, CXCL10 i CXCL11 su se pokazali kao valjani biomarkeri za razvoj srčane insuficijencije i disfunkcije lijeve komore, što ukazuje na potcrtavajući patofiziološki odnos između nivoa ovih hemokina i razvoja nepovoljnog remodeliranja srca.^{[12] [13]}

Klinički značaj

Osnovni nivoi CXCL10 u plazmi prije tretmana su povišeni kod pacijenata hronično inficiranih virusom hepatitisa C (HCV) genotipova 1 ili 4 koji ne postižu trajni virusni odgovor (SVR) nakon završetka antivirusne terapije.^[14][15] CXCL10 u plazmi sispoljava se u svojoj unutarjetrenoj iRNK, a oboje upečatljivo predviđaju prve dane eliminacije HCV RNK („opadanje prve faze“) tokom terapije interferonom/ribavirinom za sve HCV genotipove.^[16] Ovo se također odnosi na pacijente koinficirane HIV-om, gdje nivoi IP-10 prije tretmana ispod 150 pg/mL predviđaju povoljan odgovor i stoga mogu biti korisni u ohrabrivanju ovih inače teško liječivih pacijenata da započnu terapiju.^[17] Patogen Leishmania major ima proteazu, GP63, koja cijepa CXCL10, implicirajući CXCL10 u odbrambene mehanizme domaćina određenih unutarćelijskih patogena, poput Leishmania.^[18]

Reference

1. GRCh38: Ensembl release 89: ENSG00000169245 - Ensembl, maj 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034855 - 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. Luster AD, Unkeless JC, Ravetch JV (1985). "Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins". Nature. 315 (6021): 672–6. Bibcode:1985Natur.315..672L. doi:10.1038/315672a0. PMID 3925348. S2CID 4358066.
6. Luster AD, Jhanwar SC, Chaganti RS, Kersey JH, Ravetch JV (maj 1987). "Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells". Proceedings of the National Academy of Sciences of the United States of America. 84 (9): 2868–71. Bibcode:1987PNAS...84.2868L. doi:10.1073/pnas.84.9.2868. PMC 304761. PMID 2437586.
7. "UniProt, P02778" (jezik: engleski). Pristupljeno 24. 10. 2021.
8. Swaminathan GJ, Holloway DE, Colvin RA, Campanella GK, Papageorgiou AC, Luster AD, Acharya KR (maj 2003). "Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine". Structure. 11 (5): 521–32. doi:10.1016/S0969-2126(03)00070-4. PMID 12737818.
9. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (april 2002). "IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking". Journal of Immunology. 168 (7): 3195–204. doi:10.4049/jimmunol.168.7.3195. PMID 11907072.
10. Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, et al. (juli 1995). "Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo". The Journal of Experimental Medicine. 182 (1): 155–62. doi:10.1084/jem.182.1.155. PMC 2192108. PMID 7540647.
11. Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD (august 2002). "The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions". Biochemistry. 41 (33): 10418–25. doi:10.1021/bi026020q. PMID 12173928.
12. Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM (2015). "Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study". PLOS ONE. 10 (10): e0141394. Bibcode:2015PLoSO..1041394A. doi:10.1371/journal.pone.0141394. PMC 4624781. PMID 26506526.
13. Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, et al. (august 2016). "CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study". Journal of Cardiovascular Translational Research. 9 (4): 302–14. doi:10.1007/s12265-016-9703-3. PMID 27271043. S2CID 41188765.
14. Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, et al. (oktobar 2006). "Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection". The Journal of Infectious Diseases. 194 (7): 895–903. doi:10.1086/507307. PMID 16960776.
15. Lagging M, Romero AI, Westin J, Norkrans G, Dhillon AP, Pawlotsky JM, et al. (decembar 2006). "IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection". Hepatology. 44 (6): 1617–25. doi:10.1002/hep.21407. PMID 17133471. S2CID 27733803.
16. Askarieh G, Alsiö A, Pugnale P, Negro F, Ferrari C, Neumann AU, et al. (maj 2010). "Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C". Hepatology. 51 (5): 1523–30. doi:10.1002/hep.23509. PMID 20186843. S2CID 205873437.
17. Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M (decembar 2010). "IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV". Scandinavian Journal of Infectious Diseases. 42 (11–12): 896–901. doi:10.3109/00365548.2010.498019. PMID 20608766. S2CID 28542340.
18. Antonia AL, Gibbs KD, Trahair ED, Pittman KJ, Martin AT, Schott BH, et al. (2019). "Pathogen Evasion of Chemokine Response Through Suppression of CXCL10". Frontiers in Cellular and Infection Microbiology. 9: 280. doi:10.3389/fcimb.2019.00280. PMC 6693555. PMID 31440475.

Dopunska literatura

• Farber JM (mart 1997). "Mig and IP-10: CXC chemokines that target lymphocytes". Journal of Leukocyte Biology. 61 (3): 246–57. doi:10.1002/jlb.61.3.246. PMID 9060447. S2CID 14935171.
• Neville LF, Mathiak G, Bagasra O (septembar 1997). "The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily". Cytokine & Growth Factor Reviews. 8 (3): 207–19. doi:10.1016/S1359-6101(97)00015-4. PMID 9462486.

Vanjskik linkovi

• Lokacija ljudskog genoma C7 i stranica sa detaljima o genu C7 u UCSC Genome Browseru.
• Lokacija ljudskog genoma CXCL10 i stranica sa detaljima o genu CXCL10 u UCSC Genome Browseru.
• P02778