CX3CL1

Fractalkine also known as chemokine (C-X3-C motif) ligand 1 is a protein that in humans is encoded by the CX3CL1 gene.

CX3CL1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1B2T, 1F2L, 3ONA, 4XT1, 4XT3
Identifiers
Aliases	CX3CL1, ABCD-3, C3Xkine, CXC3, CXC3C, NTN, NTT, SCYD1, fractalkine, neurotactin, C-X3-C motif chemokine ligand 1
External IDs	OMIM: 601880 MGI: 1097153 HomoloGene: 2251 GeneCards: CX3CL1
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q21 Start 57,372,477 bp[1] End 57,385,044 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 C5|8 46.79 cM Start 94,772,009 bp[2] End 94,782,427 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • cytokine activity • chemokine activity • GO:0001948 protein binding • CCR chemokine receptor binding • receptor binding • integrin binding • CX3C chemokine receptor binding Cellular component • integral component of membrane • membrane • cell membrane • extracellular region • cell surface • extracellular Biological process • G-protein coupled receptor signaling pathway • defense response • positive regulation of inflammatory response • monocyte chemotaxis • cytokine-mediated signaling pathway • chemokine-mediated signaling pathway • angiogenesis involved in wound healing • cellular response to tumor necrosis factor • wound healing • leukocyte chemotaxis • neutrophil chemotaxis • positive regulation of angiogenesis • positive regulation of transforming growth factor beta1 production • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • cell adhesion • immune response • cellular response to interleukin-1 • leukocyte adhesive activation • positive regulation of ERK1 and ERK2 cascade • cellular response to interferon-gamma • cell chemotaxis • lymphocyte chemotaxis • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand • positive regulation of calcium-independent cell-cell adhesion • chemotaxis • integrin activation • negative regulation of cell migration • leukocyte migration involved in inflammatory response • macrophage chemotaxis • regulation of receptor activity Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6376	20312
Ensembl	ENSG00000006210	ENSMUSG00000031778
UniProt	P78423	O35188
RefSeq (mRNA)	NM_002996 NM_001304392	NM_009142
RefSeq (protein)	NP_001291321 NP_002987	NP_033168
Location (UCSC)	Chr 16: 57.37 – 57.39 Mb	Chr 8: 94.77 – 94.78 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Fractalkine 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).[5][6] The polypeptide structure of CX3CL1 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.[6] CX3CL1 elicits its adhesive and migratory functions by interacting with the chemokine receptor CX3CR1.[7] Its gene is located on human chromosome 16 along with some CC chemokines known as CCL17 and CCL22.[6][8]

Fractalkine is found commonly throughout the brain, particularly in neural cells, and its receptor is known to be present on microglial cells. It has also been found to be essential for microglial cell migration.[9] CX3CL1 is also up-regulated in the hippocampus during a brief temporal window following spatial learning, the purpose of which may be to regulate glutamate-mediated neurotransmission tone. This indicates a possible role for the chemokine in the protective plasticity process of synaptic scaling.[10]

References

1. GRCh38: Ensembl release 89: ENSG00000006210 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031778 - Ensembl, May 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. Pan Y, Lloyd C, Zhou H, Dolich S, Deeds J, Gonzalo JA, Vath J, Gosselin M, Ma J, Dussault B, Woolf E, Alperin G, Culpepper J, Gutierrez-Ramos JC, Gearing D (1997). "Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation". Nature. 387 (6633): 611–617. doi:10.1038/42491. PMID 9177350.
6. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997). "A new class of membrane-bound chemokine with a CX3C motif". Nature. 385 (6617): 640–644. doi:10.1038/385640a0. PMID 9024663.
7. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (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.
8. Nomiyama H, 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.
9. Maciejewski-Lenoir, D.; Chen, S.; Feng, L.; Maki, R.; Bacon, K. B. (1999-08-01). "Characterization of fractalkine in rat brain cells: migratory and activation signals for CX3CR-1-expressing microglia". Journal of Immunology. 163 (3): 1628–1635. ISSN 0022-1767. PMID 10415068.
10. Sheridan GK, Wdowicz A, Pickering M, Watters O, Halley P, O'Sullivan NC, Mooney C, O'Connell DJ, O'Connor JJ, Murphy KJ (2014). "CX3CL1 is up-regulated in the rat hippocampus during memory-associated synaptic plasticity". Front Cell Neurosci. 8: 233. doi:10.3389/fncel.2014.00233. PMC 4130185. PMID 25161610.

External links

• Human CX3CL1 genome location and CX3CL1 gene details page in the UCSC Genome Browser.

Further reading

• Umehara H, Bloom ET, Okazaki T, Nagano Y, Yoshie O, Imai T (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, Jin ZX, Huang CR, Dong L, Kawanami T, Karasawa H, Masaki Y, Fukushima T, Hirose Y, Okazaki T (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, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (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, Dolich S, Deeds J, Gonzalo JA, Vath J, Gosselin M, Ma J, Dussault B, Woolf E, Alperin G, Culpepper J, Gutierrez-Ramos JC, Gearing D (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, Suyama A, Sugano S (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, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (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, 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): 10–1. doi:10.1159/000015000. PMID 9691168.
• Combadiere C, Salzwedel K, Smith ED, Tiffany HL, Berger EA, Murphy PM (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, Bushell TJ, Gray PW, Miller RJ (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.
• 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, Yamada N, Kawamura T, Fitzhugh DJ, Saraf MA, Schall T, Blauvelt A, Rosen SD, Hwang ST (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, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD (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, James HJ, Guo H, Brooks A, Bal H, Kinnear SA, Fine S, Epstein LG, Dairaghi D, Schall TJ, Gendelman HE, Dewhurst S, Sharer LR, Gelbard HA (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. doi:10.4049/jimmunol.164.3.1333. PMID 10640747.
• Faure S, Meyer L, Costagliola D, Vaneensberghe C, Genin E, Autran B, Delfraissy JF, McDermott DH, Murphy PM, Debré P, Théodorou I, Combadière C (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.
• Papadopoulos EJ, Fitzhugh DJ, Tkaczyk C, Gilfillan AM, Sassetti C, Metcalfe DD, Hwang ST (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, Jewell DP, Gordon S, Powrie F, Greaves DR (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.
• Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW (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.