CX3CL1

Chemokine (C-X3-C motif) ligand 1
PDB rendering based on 1b2t.
Available structures PDB 1B2T, 1F2L
Identifiers
Symbols	CX3CL1; ABCD-3; C3Xkine; CXC3; CXC3C; NTN; NTT; SCYD1; fractalkine; neurotactin
External IDs	OMIM: 601880 MGI: 1097153 HomoloGene: 2251 GeneCards: CX3CL1 Gene
Gene Ontology Molecular function • receptor binding • protein binding • chemokine activity Cellular component • extracellular region • extracellular space • plasma membrane • cell surface • integral to membrane Biological process • chemotaxis • defense response • immune response • cell adhesion • cytokine-mediated signaling pathway • neutrophil chemotaxis • leukocyte chemotaxis • positive regulation of transforming growth factor-beta1 production • negative regulation of apoptosis • positive regulation of angiogenesis • macrophage chemotaxis • lymphocyte chemotaxis • positive regulation of inflammatory response • leukocyte adhesive activation • positive regulation of calcium-independent cell-cell adhesion • angiogenesis involved in wound healing Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6376	20312
Ensembl	ENSG00000006210	ENSMUSG00000031778
UniProt	P78423	Q8C9Y1
RefSeq (mRNA)	NM_002996.3	NM_009142.3
RefSeq (protein)	NP_002987.1	NP_033168.2
Location (UCSC)	Chr 16: 57.41 – 57.42 Mb	Chr 8: 97.3 – 97.31 Mb
PubMed search	[1]	[2]

Chemokine (C-X3-C motif) ligand 1 (CX3CL1) is a large cytokine protein of 373 amino acids, it contains multiple domains and is the only known member of the CX₃C chemokine family. It is also commonly known under the names fractalkine (in humans) and neurotactin (in mice).^[1][2] The polypeptide structure of CXC3L1 differs from the typical structure of other chemokines. For example, the spacing of the characteristic N-terminal cysteines differs; there are three amino acids separating the initial pair of cysteines in CX3CL1, with none in CC chemokines and only one intervening amino acid in CXC chemokines. CX3CL1 is produced as a long protein (with 373-amino acid in humans) with an extended mucin-like stalk and a chemokine domain on top. The mucin-like stalk permits it to bind to the surface of certain cells. However a soluble (90 kD) version of this chemokine has also been observed. Soluble CX3CL1 potently chemoattracts T cells and monocytes, while the cell-bound chemokine promotes strong adhesion of leukocytes to activated endothelial cells, where it is primarily expressed.^[2] CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.^[3] Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.^[2][4]

References

1. ^ Pan, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, Vath J, Gosselin M et al. (1997). "Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation". Nature 387 (6633): 611–617. doi:10.1038/42491. PMID 9177350. 
2. ^ ^{a b c} Bazan, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A et al. (1997). "A new class of membrane-bound chemokine with a CX3C motif". Nature 385 (6617): 640–644. doi:10.1038/385640a0. PMID 9024663. 
3. ^ Imai, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S et al. (1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell 91 (4): 521–530. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561. 
4. ^ Nomiyama, Imai T, Kusuda J, Miura R, Callen DF, Yoshie O (1998). "Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13". Cytogenet. Cell Genet 81 (1): 10–11. doi:10.1159/000015000. PMID 9691168. 

Further reading

• Umehara H, Bloom ET, Okazaki T, et al. (2004). "Fractalkine in vascular biology: from basic research to clinical disease". Arterioscler. Thromb. Vasc. Biol. 24 (1): 34–40. doi:10.1161/01.ATV.0000095360.62479.1F. PMID 12969992. 
• Umehara H, Tanaka M, Sawaki T, et al. (2006). "Fractalkine in rheumatoid arthritis and allied conditions". Mod Rheumatol 16 (3): 124–30. doi:10.1007/s10165-006-0471-9. PMID 16767549. 
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• Bazan JF, Bacon KB, Hardiman G, et al. (1997). "A new class of membrane-bound chemokine with a CX3C motif". Nature 385 (6617): 640–4. doi:10.1038/385640a0. PMID 9024663. 
• Pan Y, Lloyd C, Zhou H, et al. (1997). "Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation". Nature 387 (6633): 611–7. doi:10.1038/42491. PMID 9177350. 
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• Imai T, Hieshima K, Haskell C, et al. (1997). "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion". Cell 91 (4): 521–30. doi:10.1016/S0092-8674(00)80438-9. PMID 9390561. 
• Nomiyama H, Imai T, Kusuda J, et al. (1998). "Human chemokines fractalkine (SCYD1), MDC (SCYA22) and TARC (SCYA17) are clustered on chromosome 16q13". Cytogenet. Cell Genet. 81 (1): 10–1. doi:10.1159/000015000. PMID 9691168. 
• Combadiere C, Salzwedel K, Smith ED, et al. (1998). "Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1". J. Biol. Chem. 273 (37): 23799–804. doi:10.1074/jbc.273.37.23799. PMID 9726990. 
• Meucci O, Fatatis A, Simen AA, et al. (1998). "Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity". Proc. Natl. Acad. Sci. U.S.A. 95 (24): 14500–5. doi:10.1073/pnas.95.24.14500. PMC 24402. PMID 9826729. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24402. 
• Mizoue LS, Bazan JF, Johnson EC, Handel TM (1999). "Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1". Biochemistry 38 (5): 1402–14. doi:10.1021/bi9820614. PMID 9931005. 
• Papadopoulos EJ, Sassetti C, Saeki H, et al. (1999). "Fractalkine, a CX3C chemokine, is expressed by dendritic cells and is up-regulated upon dendritic cell maturation". Eur. J. Immunol. 29 (8): 2551–9. doi:10.1002/(SICI)1521-4141(199908)29:08<2551::AID-IMMU2551>3.0.CO;2-T. PMID 10458770. 
• Loftus BJ, Kim UJ, Sneddon VP, et al. (1999). "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics 60 (3): 295–308. doi:10.1006/geno.1999.5927. PMID 10493829. 
• Tong N, Perry SW, Zhang Q, et al. (2000). "Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system". J. Immunol. 164 (3): 1333–9. PMID 10640747. 
• Faure S, Meyer L, Costagliola D, et al. (2000). "Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1". Science 287 (5461): 2274–7. doi:10.1126/science.287.5461.2274. PMID 10731151. 
• Hoover DM, Mizoue LS, Handel TM, Lubkowski J (2000). "The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement". J. Biol. Chem. 275 (30): 23187–93. doi:10.1074/jbc.M002584200. PMID 10770945. 
• Meucci O, Fatatis A, Simen AA, Miller RJ (2000). "Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival". Proc. Natl. Acad. Sci. U.S.A. 97 (14): 8075–80. doi:10.1073/pnas.090017497. PMC 16672. PMID 10869418. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=16672. 
• Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, et al. (2000). "Mast cells migrate, but do not degranulate, in response to fractalkine, a membrane-bound chemokine expressed constitutively in diverse cells of the skin". Eur. J. Immunol. 30 (8): 2355–61. doi:10.1002/1521-4141(2000)30:8<2355::AID-IMMU2355>3.0.CO;2-#. PMID 10940926. 
• Lucas AD, Chadwick N, Warren BF, et al. (2001). "The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo". Am. J. Pathol. 158 (3): 855–66. doi:10.1016/S0002-9440(10)64034-5. PMC 1850344. PMID 11238035. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1850344. 
• Garton KJ, Gough PJ, Blobel CP, et al. (2001). "Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1)". J. Biol. Chem. 276 (41): 37993–8001. doi:10.1074/jbc.M106434200. PMID 11495925.