X3CL1_HUMAN
ID X3CL1_HUMAN Reviewed; 397 AA.
AC P78423; O00672;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Fractalkine {ECO:0000303|PubMed:23125415};
DE AltName: Full=C-X3-C motif chemokine 1 {ECO:0000303|PubMed:9024663};
DE AltName: Full=CX3C membrane-anchored chemokine {ECO:0000303|PubMed:9024663};
DE AltName: Full=Neurotactin {ECO:0000303|PubMed:9177350};
DE AltName: Full=Small-inducible cytokine D1;
DE Contains:
DE RecName: Full=Processed fractalkine;
DE Flags: Precursor;
GN Name=CX3CL1 {ECO:0000303|PubMed:9024663};
GN Synonyms=FKN {ECO:0000303|PubMed:23125415},
GN NTT {ECO:0000303|PubMed:9177350}, SCYD1; ORFNames=A-152E5.2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=9177350; DOI=10.1038/42491;
RA Pan Y., Lloyd C., Zhou H., Dolich S., Deeds J., Gonzalo J.-A., Vath J.,
RA Gosselin M., Ma J., Dussault B., Woolf E., Alperin G., Culpepper J.,
RA Gutierrez-Ramos J.-C., Gearing D.P.;
RT "Neurotactin, a membrane-anchored chemokine upregulated in brain
RT inflammation.";
RL Nature 387:611-617(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, PROTEOLYTIC
RP CLEAVAGE, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=9024663; DOI=10.1038/385640a0;
RA Bazan J.F., Bacon K.B., Hardiman G., Wang W., Soo K., Rossi D.,
RA Greaves D.R., Zlotnik A., Schall T.J.;
RT "A new class of membrane-bound chemokine with a CX3C motif.";
RL Nature 385:640-644(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=9782118; DOI=10.1084/jem.188.8.1413;
RA Fong A.M., Robinson L.A., Steeber D.A., Tedder T.F., Yoshie O., Imai T.,
RA Patel D.D.;
RT "Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture,
RT firm adhesion, and activation under physiologic flow.";
RL J. Exp. Med. 188:1413-1419(1998).
RN [6]
RP FUNCTION.
RX PubMed=12055230; DOI=10.4049/jimmunol.168.12.6173;
RA Nishimura M., Umehara H., Nakayama T., Yoneda O., Hieshima K., Kakizaki M.,
RA Dohmae N., Yoshie O., Imai T.;
RT "Dual functions of fractalkine/CX3C ligand 1 in trafficking of
RT perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by
RT CX3CR1 expression.";
RL J. Immunol. 168:6173-6180(2002).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT SER-253 AND THR-329, AND STRUCTURE
RP OF CARBOHYDRATES.
RC TISSUE=Cerebrospinal fluid;
RX PubMed=19838169; DOI=10.1038/nmeth.1392;
RA Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G.,
RA Larson G.;
RT "Enrichment of glycopeptides for glycan structure and attachment site
RT identification.";
RL Nat. Methods 6:809-811(2009).
RN [8]
RP GLYCOSYLATION AT THR-183; SER-253 AND THR-329, STRUCTURE OF CARBOHYDRATES,
RP AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22171320; DOI=10.1074/mcp.m111.013649;
RA Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.;
RT "Human urinary glycoproteomics; attachment site specific analysis of N- and
RT O-linked glycosylations by CID and ECD.";
RL Mol. Cell. Proteomics 11:1-17(2012).
RN [9]
RP FUNCTION, BINDING TO CX3CR1 AND INTEGRINS, IDENTIFICATION IN A COMPLEX WITH
RP CX3CR1 AND INTEGRINS, AND MUTAGENESIS OF LYS-60; ARG-61; ARG-71; LYS-78 AND
RP LYS-83.
RX PubMed=23125415; DOI=10.4049/jimmunol.1200889;
RA Fujita M., Takada Y.K., Takada Y.;
RT "Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine,
RT and the integrin-binding defective mutant of fractalkine is an antagonist
RT of CX3CR1.";
RL J. Immunol. 189:5809-5819(2012).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=23765988; DOI=10.1002/jcp.24418;
RA Caballero-Campo P., Buffone M.G., Benencia F., Conejo-Garcia J.R.,
RA Rinaudo P.F., Gerton G.L.;
RT "A role for the chemokine receptor CCR6 in mammalian sperm motility and
RT chemotaxis.";
RL J. Cell. Physiol. 229:68-78(2014).
RN [11]
RP FUNCTION, BINDING TO INTEGRINS, AND MUTAGENESIS OF LYS-60 AND ARG-61.
RX PubMed=24789099; DOI=10.1371/journal.pone.0096372;
RA Fujita M., Takada Y.K., Takada Y.;
RT "The chemokine fractalkine can activate integrins without CX3CR1 through
RT direct binding to a ligand-binding site distinct from the classical RGD-
RT binding site.";
RL PLoS ONE 9:E96372-E96372(2014).
RN [12]
RP STRUCTURE BY NMR OF 25-100, SUBUNIT, AND BINDING TO CX3CR1.
RX PubMed=9931005; DOI=10.1021/bi9820614;
RA Mizoue L.S., Bazan J.F., Johnson E.C., Handel T.M.;
RT "Solution structure and dynamics of the CX3C chemokine domain of
RT fractalkine and its interaction with an N-terminal fragment of CX3CR1.";
RL Biochemistry 38:1402-1414(1999).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 25-98, AND DISULFIDE BONDS.
RX PubMed=10770945; DOI=10.1074/jbc.m002584200;
RA Hoover D.M., Mizoue L.S., Handel T.M., Lubkowski J.;
RT "The crystal structure of the chemokine domain of fractalkine shows a novel
RT quaternary arrangement.";
RL J. Biol. Chem. 275:23187-23193(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-100 IN COMPLEX WITH POX VIRUS
RP CRMD, FUNCTION, AND INTERACTION WITH VIRAL CRMD.
RX PubMed=21829356; DOI=10.1371/journal.ppat.1002162;
RA Xue X., Lu Q., Wei H., Wang D., Chen D., He G., Huang L., Wang H., Wang X.;
RT "Structural basis of chemokine sequestration by CrmD, a poxvirus-encoded
RT tumor necrosis factor receptor.";
RL PLoS Pathog. 7:E1002162-E1002162(2011).
RN [15] {ECO:0007744|PDB:4XT1, ECO:0007744|PDB:4XT3}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS) OF 25-101, AND INTERACTION WITH
RP HHV-5 US28 (MICROBIAL INFECTION).
RX PubMed=25745166; DOI=10.1126/science.aaa5026;
RA Burg J.S., Ingram J.R., Venkatakrishnan A.J., Jude K.M., Dukkipati A.,
RA Feinberg E.N., Angelini A., Waghray D., Dror R.O., Ploegh H.L.,
RA Garcia K.C.;
RT "Structural basis for chemokine recognition and activation of a viral G
RT protein-coupled receptor.";
RL Science 347:1113-1117(2015).
RN [16] {ECO:0007744|PDB:5WB2}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 34-100.
RX PubMed=29882741; DOI=10.7554/elife.35850;
RA Miles T.F., Spiess K., Jude K.M., Tsutsumi N., Burg J.S., Ingram J.R.,
RA Waghray D., Hjorto G.M., Larsen O., Ploegh H.L., Rosenkilde M.M.,
RA Garcia K.C.;
RT "Viral GPCR US28 can signal in response to chemokine agonists of nearly
RT unlimited structural degeneracy.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Chemokine that acts as a ligand for both CX3CR1 and integrins
CC ITGAV:ITGB3 and ITGA4:ITGB1 (PubMed:9782118, PubMed:12055230,
CC PubMed:23125415, PubMed:9931005, PubMed:21829356). The CX3CR1-CX3CL1
CC signaling exerts distinct functions in different tissue compartments,
CC such as immune response, inflammation, cell adhesion and chemotaxis
CC (PubMed:9024663, PubMed:9177350, PubMed:9782118, PubMed:12055230).
CC Regulates leukocyte adhesion and migration processes at the endothelium
CC (PubMed:9024663, PubMed:9177350). Can activate integrins in both a
CC CX3CR1-dependent and CX3CR1-independent manner (PubMed:23125415,
CC PubMed:24789099). In the presence of CX3CR1, activates integrins by
CC binding to the classical ligand-binding site (site 1) in integrins
CC (PubMed:23125415, PubMed:24789099). In the absence of CX3CR1, binds to
CC a second site (site 2) in integrins which is distinct from site 1 and
CC enhances the binding of other integrin ligands to site 1
CC (PubMed:23125415, PubMed:24789099). {ECO:0000269|PubMed:12055230,
CC ECO:0000269|PubMed:21829356, ECO:0000269|PubMed:23125415,
CC ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:9024663,
CC ECO:0000269|PubMed:9177350, ECO:0000269|PubMed:9782118,
CC ECO:0000269|PubMed:9931005}.
CC -!- FUNCTION: [Processed fractalkine]: The soluble form is chemotactic for
CC T-cells and monocytes, but not for neutrophils.
CC {ECO:0000269|PubMed:9024663}.
CC -!- FUNCTION: [Fractalkine]: The membrane-bound form promotes adhesion of
CC those leukocytes to endothelial cells. {ECO:0000269|PubMed:9024663}.
CC -!- SUBUNIT: Monomer (PubMed:9931005). Forms a ternary complex with CX3CR1
CC and ITGAV:ITGB3 or ITGA4:ITGB1 (PubMed:23125415).
CC {ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:9931005}.
CC -!- SUBUNIT: (Microbial infection) Interacts with pox virus crmD; this
CC inhibits cell migration mediated by CX3CL1.
CC {ECO:0000269|PubMed:21829356}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via N-terminus) with human
CC cytomegalovirus (HHV-5) US28. {ECO:0000269|PubMed:25745166}.
CC -!- INTERACTION:
CC P78423; P05556: ITGB1; NbExp=2; IntAct=EBI-15188013, EBI-703066;
CC P78423; P05106: ITGB3; NbExp=7; IntAct=EBI-15188013, EBI-702847;
CC P78423; P69332: US28; Xeno; NbExp=4; IntAct=EBI-15188013, EBI-16147206;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9024663};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Processed fractalkine]: Secreted
CC {ECO:0000269|PubMed:9024663}.
CC -!- TISSUE SPECIFICITY: Expressed in the seminal plasma, endometrial fluid
CC and follicular fluid (at protein level). Small intestine, colon,
CC testis, prostate, heart, brain, lung, skeletal muscle, kidney and
CC pancreas. Most abundant in the brain and heart.
CC {ECO:0000269|PubMed:23765988, ECO:0000269|PubMed:9024663,
CC ECO:0000269|PubMed:9177350}.
CC -!- INDUCTION: By TNF and IL1/interleukin-1 in pulmonary endothelial cells
CC and umbilical vein endothelial cells. {ECO:0000269|PubMed:9024663}.
CC -!- PTM: A soluble short 95 kDa form may be released by proteolytic
CC cleavage from the long membrane-anchored form.
CC {ECO:0000269|PubMed:9024663}.
CC -!- PTM: O-glycosylated with core 1 or possibly core 8 glycans.
CC {ECO:0000269|PubMed:19838169, ECO:0000269|PubMed:22171320}.
CC -!- SIMILARITY: Belongs to the intercrine delta family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CX3CL1 entry;
CC URL="https://en.wikipedia.org/wiki/CX3CL1";
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DR EMBL; U91835; AAB50014.1; -; mRNA.
DR EMBL; U84487; AAB49679.1; -; mRNA.
DR EMBL; AC004382; AAC24307.1; -; Genomic_DNA.
DR EMBL; BC001163; AAH01163.1; -; mRNA.
DR EMBL; BC016164; AAH16164.1; -; mRNA.
DR CCDS; CCDS10779.1; -.
DR RefSeq; NP_002987.1; NM_002996.4.
DR PDB; 1B2T; NMR; -; A=25-100.
DR PDB; 1F2L; X-ray; 2.00 A; A/B/C/D=25-98.
DR PDB; 3ONA; X-ray; 2.60 A; B=24-100.
DR PDB; 4XT1; X-ray; 2.89 A; B=26-101.
DR PDB; 4XT3; X-ray; 3.80 A; B=26-101.
DR PDB; 5WB2; X-ray; 3.50 A; B=34-100.
DR PDB; 7RKF; EM; 4.00 A; L=25-101.
DR PDB; 7RKM; EM; 3.50 A; L=25-101.
DR PDB; 7RKN; EM; 3.60 A; L=25-101.
DR PDBsum; 1B2T; -.
DR PDBsum; 1F2L; -.
DR PDBsum; 3ONA; -.
DR PDBsum; 4XT1; -.
DR PDBsum; 4XT3; -.
DR PDBsum; 5WB2; -.
DR PDBsum; 7RKF; -.
DR PDBsum; 7RKM; -.
DR PDBsum; 7RKN; -.
DR AlphaFoldDB; P78423; -.
DR SMR; P78423; -.
DR BioGRID; 112278; 72.
DR DIP; DIP-5878N; -.
DR IntAct; P78423; 12.
DR STRING; 9606.ENSP00000006053; -.
DR ChEMBL; CHEMBL4630883; -.
DR GlyConnect; 698; 1 N-Linked glycan (1 site), 4 O-Linked glycans (4 sites).
DR GlyGen; P78423; 9 sites, 1 N-linked glycan (1 site), 5 O-linked glycans (8 sites).
DR iPTMnet; P78423; -.
DR PhosphoSitePlus; P78423; -.
DR BioMuta; CX3CL1; -.
DR DMDM; 6175080; -.
DR MassIVE; P78423; -.
DR PaxDb; P78423; -.
DR PeptideAtlas; P78423; -.
DR PRIDE; P78423; -.
DR ProteomicsDB; 57622; -.
DR ABCD; P78423; 11 sequenced antibodies.
DR Antibodypedia; 15022; 771 antibodies from 43 providers.
DR CPTC; P78423; 3 antibodies.
DR DNASU; 6376; -.
DR Ensembl; ENST00000006053.7; ENSP00000006053.6; ENSG00000006210.7.
DR GeneID; 6376; -.
DR KEGG; hsa:6376; -.
DR MANE-Select; ENST00000006053.7; ENSP00000006053.6; NM_002996.6; NP_002987.1.
DR UCSC; uc002eli.4; human.
DR CTD; 6376; -.
DR DisGeNET; 6376; -.
DR GeneCards; CX3CL1; -.
DR HGNC; HGNC:10647; CX3CL1.
DR HPA; ENSG00000006210; Tissue enhanced (breast).
DR MIM; 601880; gene.
DR neXtProt; NX_P78423; -.
DR OpenTargets; ENSG00000006210; -.
DR PharmGKB; PA35577; -.
DR VEuPathDB; HostDB:ENSG00000006210; -.
DR eggNOG; ENOG502SNIE; Eukaryota.
DR GeneTree; ENSGT01050000244920; -.
DR InParanoid; P78423; -.
DR OrthoDB; 1060256at2759; -.
DR PhylomeDB; P78423; -.
DR TreeFam; TF337534; -.
DR PathwayCommons; P78423; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P78423; -.
DR SIGNOR; P78423; -.
DR BioGRID-ORCS; 6376; 8 hits in 1068 CRISPR screens.
DR EvolutionaryTrace; P78423; -.
DR GeneWiki; CX3CL1; -.
DR GenomeRNAi; 6376; -.
DR Pharos; P78423; Tbio.
DR PRO; PR:P78423; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P78423; protein.
DR Bgee; ENSG00000006210; Expressed in right lung and 185 other tissues.
DR ExpressionAtlas; P78423; baseline and differential.
DR Genevisible; P78423; HS.
DR GO; GO:0042995; C:cell projection; ISS:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; ISS:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; TAS:ARUK-UCL.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; IMP:ARUK-UCL.
DR GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR GO; GO:0031737; F:CX3C chemokine receptor binding; IDA:UniProtKB.
DR GO; GO:0045237; F:CXCR1 chemokine receptor binding; IPI:ARUK-UCL.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:UniProtKB.
DR GO; GO:0007568; P:aging; ISS:ARUK-UCL.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; IEA:Ensembl.
DR GO; GO:0035425; P:autocrine signaling; ISS:ARUK-UCL.
DR GO; GO:0007155; P:cell adhesion; IPI:ARUK-UCL.
DR GO; GO:0060326; P:cell chemotaxis; IDA:ARUK-UCL.
DR GO; GO:0098609; P:cell-cell adhesion; ISS:ARUK-UCL.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ARUK-UCL.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IBA:GO_Central.
DR GO; GO:0071347; P:cellular response to interleukin-1; IBA:GO_Central.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IBA:GO_Central.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:UniProtKB.
DR GO; GO:0006952; P:defense response; TAS:UniProtKB.
DR GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0006955; P:immune response; TAS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0033622; P:integrin activation; IMP:UniProtKB.
DR GO; GO:0050902; P:leukocyte adhesive activation; TAS:UniProtKB.
DR GO; GO:0030595; P:leukocyte chemotaxis; TAS:UniProtKB.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IMP:UniProtKB.
DR GO; GO:0048247; P:lymphocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0001774; P:microglial cell activation; ISS:ARUK-UCL.
DR GO; GO:0061518; P:microglial cell proliferation; IMP:ARUK-UCL.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ARUK-UCL.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:BHF-UCL.
DR GO; GO:0010812; P:negative regulation of cell-substrate adhesion; NAS:ARUK-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl.
DR GO; GO:1900450; P:negative regulation of glutamate receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0110091; P:negative regulation of hippocampal neuron apoptotic process; IGI:ARUK-UCL.
DR GO; GO:0032690; P:negative regulation of interleukin-1 alpha production; ISS:ARUK-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; TAS:ARUK-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; TAS:ARUK-UCL.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; ISS:ARUK-UCL.
DR GO; GO:2001223; P:negative regulation of neuron migration; TAS:ARUK-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IDA:ARUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; ISS:ARUK-UCL.
DR GO; GO:0016322; P:neuron remodeling; TAS:ARUK-UCL.
DR GO; GO:0030593; P:neutrophil chemotaxis; IBA:GO_Central.
DR GO; GO:0050918; P:positive chemotaxis; IMP:ARUK-UCL.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; IGI:ARUK-UCL.
DR GO; GO:0051041; P:positive regulation of calcium-independent cell-cell adhesion; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:ARUK-UCL.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; TAS:ARUK-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISS:ARUK-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; IGI:ARUK-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IGI:ARUK-UCL.
DR GO; GO:1904141; P:positive regulation of microglial cell migration; IDA:ARUK-UCL.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISS:ARUK-UCL.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IGI:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IGI:ARUK-UCL.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; IGI:ARUK-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; IEA:Ensembl.
DR GO; GO:0031664; P:regulation of lipopolysaccharide-mediated signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0050767; P:regulation of neurogenesis; TAS:ARUK-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; TAS:ARUK-UCL.
DR GO; GO:0002931; P:response to ischemia; ISS:ARUK-UCL.
DR GO; GO:0098883; P:synapse pruning; TAS:ARUK-UCL.
DR CDD; cd00274; Chemokine_CX3C; 1.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR034127; Chemokine_CX3C.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR008097; CX3CL1.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; PTHR12015; 1.
DR PANTHER; PTHR12015:SF92; PTHR12015:SF92; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell adhesion; Cell membrane; Chemotaxis; Cytokine;
KW Disulfide bond; Glycoprotein; Host-virus interaction;
KW Inflammatory response; Membrane; Reference proteome; Secreted; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT CHAIN 25..397
FT /note="Fractalkine"
FT /id="PRO_0000005252"
FT CHAIN 25..?339
FT /note="Processed fractalkine"
FT /id="PRO_0000296224"
FT TOPO_DOM 25..341
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..397
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 25..100
FT /note="Chemokine and involved in interaction with
FT ITGAV:ITGB3 and ITGA4:ITGB1"
FT /evidence="ECO:0000269|PubMed:23125415"
FT REGION 101..341
FT /note="Mucin-like stalk"
FT REGION 128..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..309
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 130..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 214..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 289..303
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 339..340
FT /note="Cleavage; to produce soluble form"
FT /evidence="ECO:0000255"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 183
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:22171320"
FT CARBOHYD 253
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:22171320"
FT CARBOHYD 329
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19838169,
FT ECO:0000269|PubMed:22171320"
FT DISULFID 32..58
FT /evidence="ECO:0000269|PubMed:10770945"
FT DISULFID 36..74
FT /evidence="ECO:0000269|PubMed:10770945"
FT VARIANT 240
FT /note="A -> V (in dbSNP:rs35860084)"
FT /id="VAR_048714"
FT MUTAGEN 60
FT /note="K->A: Reduced binding to integrin ITGAV:ITGB3, but
FT no effect on binding to CX3CR1; when associated with A-61."
FT /evidence="ECO:0000269|PubMed:23125415"
FT MUTAGEN 60
FT /note="K->E: Dominant-negative mutant, reduced binding to
FT integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding
FT to CX3CR1, defective in ternary complex formation, integrin
FT activation and fractalkine signaling and suppression of
FT leukocyte recruitment in the peritonitis model in vivo;
FT when associated with E-61."
FT /evidence="ECO:0000269|PubMed:23125415,
FT ECO:0000269|PubMed:24789099"
FT MUTAGEN 61
FT /note="R->A: Reduced binding to integrin ITGAV:ITGB3, but
FT no effect on binding to CX3CR1; when associated with A-60."
FT /evidence="ECO:0000269|PubMed:23125415"
FT MUTAGEN 61
FT /note="R->E: Dominant-negative mutant, reduced binding to
FT integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding
FT to CX3CR1, defective in ternary complex formation, integrin
FT activation and fractalkine signaling and suppression of
FT leukocyte recruitment in the peritonitis model in vivo;
FT when associated with E-60."
FT /evidence="ECO:0000269|PubMed:23125415,
FT ECO:0000269|PubMed:24789099"
FT MUTAGEN 71
FT /note="R->A: Loss of binding to CX3CR1 and ability to
FT induce chemotaxis but no effect on binding to integrins."
FT /evidence="ECO:0000269|PubMed:23125415"
FT MUTAGEN 78
FT /note="K->A: Little or no effect on binding to integrin
FT ITGAV:ITGB3."
FT /evidence="ECO:0000269|PubMed:23125415"
FT MUTAGEN 78
FT /note="K->A: Little or no effect on binding to integrin
FT ITGAV:ITGB3; when associated with A-83."
FT /evidence="ECO:0000269|PubMed:23125415"
FT MUTAGEN 83
FT /note="K->A: Little or no effect on binding to integrin
FT ITGAV:ITGB3; when associated with A-78."
FT /evidence="ECO:0000269|PubMed:23125415"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:7RKM"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:1F2L"
FT HELIX 45..47
FT /evidence="ECO:0007829|PDB:1F2L"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:1F2L"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:1F2L"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:3ONA"
FT STRAND 63..67
FT /evidence="ECO:0007829|PDB:1F2L"
FT TURN 68..70
FT /evidence="ECO:0007829|PDB:3ONA"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:1F2L"
FT HELIX 80..90
FT /evidence="ECO:0007829|PDB:1F2L"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:1F2L"
SQ SEQUENCE 397 AA; 42203 MW; BAC71F5080DF9CA6 CRC64;
MAPISLSWLL RLATFCHLTV LLAGQHHGVT KCNITCSKMT SKIPVALLIH YQQNQASCGK
RAIILETRQH RLFCADPKEQ WVKDAMQHLD RQAAALTRNG GTFEKQIGEV KPRTTPAAGG
MDESVVLEPE ATGESSSLEP TPSSQEAQRA LGTSPELPTG VTGSSGTRLP PTPKAQDGGP
VGTELFRVPP VSTAATWQSS APHQPGPSLW AEAKTSEAPS TQDPSTQAST ASSPAPEENA
PSEGQRVWGQ GQSPRPENSL EREEMGPVPA HTDAFQDWGP GSMAHVSVVP VSSEGTPSRE
PVASGSWTPK AEEPIHATMD PQRLGVLITP VPDAQAATRR QAVGLLAFLG LLFCLGVAMF
TYQSLQGCPR KMAGEMAEGL RYIPRSCGSN SYVLVPV
