X3CL1_RAT
ID X3CL1_RAT Reviewed; 393 AA.
AC O55145;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 3.
DT 25-MAY-2022, entry version 138.
DE RecName: Full=Fractalkine;
DE AltName: Full=C-X3-C motif chemokine 1;
DE AltName: Full=CX3C membrane-anchored chemokine;
DE AltName: Full=Neurotactin;
DE AltName: Full=Small-inducible cytokine D1;
DE Contains:
DE RecName: Full=Processed fractalkine;
DE Flags: Precursor;
GN Name=Cx3cl1; Synonyms=Acc1, Fkn, Scyd1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=9724801; DOI=10.1073/pnas.95.18.10896;
RA Harrison J.K., Jiang Y., Chen S., Xia Y., Maciejewski D., McNamara R.K.,
RA Streit W.J., Salafranca M.N., Adhikari S., Thompson D.A., Botti P.,
RA Bacon K.B., Feng L.;
RT "Role for neuronally derived fractalkine in mediating interactions between
RT neurons and CX3CR1-expressing microglia.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:10896-10901(1998).
RN [2]
RP SEQUENCE REVISION TO 127-151.
RA Feng L., Harrison J.K.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 204-335, AND TISSUE SPECIFICITY.
RX PubMed=9845323; DOI=10.1016/s0014-5793(98)01384-2;
RA Schwaeble W.J., Stover C.M., Schall T.J., Dairaghi D.J., Trinder P.K.E.,
RA Linington C., Iglesias A., Schubart A., Lynch N.J., Weihe E.,
RA Schaefer M.K.-H.;
RT "Neuronal expression of fractalkine in the presence and absence of
RT inflammation.";
RL FEBS Lett. 439:203-207(1998).
CC -!- FUNCTION: Chemokine that acts as a ligand for both CX3CR1 and integrins
CC ITGAV:ITGB3 and ITGA4:ITGB1. The CX3CR1-CX3CL1 signaling exerts
CC distinct functions in different tissue compartments, such as immune
CC response, inflammation, cell adhesion and chemotaxis. Regulates
CC leukocyte adhesion and migration processes at the endothelium. Can
CC activate integrins in both a CX3CR1-dependent and CX3CR1-independent
CC manner. In the presence of CX3CR1, activates integrins by binding to
CC the classical ligand-binding site (site 1) in integrins. In the absence
CC of CX3CR1, binds to a second site (site 2) in integrins which is
CC distinct from site 1 and enhances the binding of other integrin ligands
CC to site 1. {ECO:0000250|UniProtKB:P78423}.
CC -!- FUNCTION: [Processed fractalkine]: The soluble form is chemotactic for
CC T-cells and monocytes, but not for neutrophils.
CC {ECO:0000250|UniProtKB:P78423}.
CC -!- FUNCTION: [Fractalkine]: The membrane-bound form promotes adhesion of
CC those leukocytes to endothelial cells. {ECO:0000250|UniProtKB:P78423}.
CC -!- SUBUNIT: Monomer. Forms a ternary complex with CX3CR1 and ITGAV:ITGB3
CC or ITGA4:ITGB1. {ECO:0000250|UniProtKB:P78423}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P78423};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Processed fractalkine]: Secreted
CC {ECO:0000250|UniProtKB:P78423}.
CC -!- TISSUE SPECIFICITY: Highest levels in brain (neurons). Significant
CC levels in kidney, heart, lung and adrenal gland.
CC {ECO:0000269|PubMed:9724801, ECO:0000269|PubMed:9845323}.
CC -!- PTM: A soluble short form may be released by proteolytic cleavage from
CC the long membrane-anchored form. {ECO:0000250|UniProtKB:P78423}.
CC -!- SIMILARITY: Belongs to the intercrine delta family. {ECO:0000305}.
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DR EMBL; AF030358; AAC33834.2; -; mRNA.
DR EMBL; Y16813; CAA76404.1; -; mRNA.
DR RefSeq; NP_604450.1; NM_134455.1.
DR AlphaFoldDB; O55145; -.
DR SMR; O55145; -.
DR BioGRID; 250131; 1.
DR STRING; 10116.ENSRNOP00000022128; -.
DR GlyGen; O55145; 1 site.
DR PaxDb; O55145; -.
DR GeneID; 89808; -.
DR KEGG; rno:89808; -.
DR UCSC; RGD:620458; rat.
DR CTD; 6376; -.
DR RGD; 620458; Cx3cl1.
DR eggNOG; ENOG502SNIE; Eukaryota.
DR InParanoid; O55145; -.
DR OrthoDB; 1060256at2759; -.
DR PhylomeDB; O55145; -.
DR Reactome; R-RNO-380108; Chemokine receptors bind chemokines.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:O55145; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0042995; C:cell projection; IDA:ARUK-UCL.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; IDA:ARUK-UCL.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098794; C:postsynapse; IEA:GOC.
DR GO; GO:0048020; F:CCR chemokine receptor binding; IBA:GO_Central.
DR GO; GO:0042056; F:chemoattractant activity; ISO:RGD.
DR GO; GO:0008009; F:chemokine activity; IDA:RGD.
DR GO; GO:0031737; F:CX3C chemokine receptor binding; ISS:UniProtKB.
DR GO; GO:0045237; F:CXCR1 chemokine receptor binding; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0060055; P:angiogenesis involved in wound healing; ISO:RGD.
DR GO; GO:0035425; P:autocrine signaling; IGI:ARUK-UCL.
DR GO; GO:0007155; P:cell adhesion; ISO:RGD.
DR GO; GO:0060326; P:cell chemotaxis; ISO:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; IDA: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; ISO:RGD.
DR GO; GO:0006935; P:chemotaxis; IDA:RGD.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0048245; P:eosinophil chemotaxis; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0060080; P:inhibitory postsynaptic potential; IMP:RGD.
DR GO; GO:0033622; P:integrin activation; ISS:UniProtKB.
DR GO; GO:0050902; P:leukocyte adhesive activation; IEA:InterPro.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; ISS:UniProtKB.
DR GO; GO:0048247; P:lymphocyte chemotaxis; ISO:RGD.
DR GO; GO:0001774; P:microglial cell activation; IDA:ARUK-UCL.
DR GO; GO:0061518; P:microglial cell proliferation; ISO:RGD.
DR GO; GO:0002548; P:monocyte chemotaxis; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0030336; P:negative regulation of cell migration; ISO:RGD.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD.
DR GO; GO:1900450; P:negative regulation of glutamate receptor signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0110091; P:negative regulation of hippocampal neuron apoptotic process; ISO:RGD.
DR GO; GO:0032690; P:negative regulation of interleukin-1 alpha production; IDA:ARUK-UCL.
DR GO; GO:1903979; P:negative regulation of microglial cell activation; IDA:ARUK-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0045906; P:negative regulation of vasoconstriction; IDA:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; IDA:ARUK-UCL.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISO:RGD.
DR GO; GO:0030168; P:platelet activation; IMP:RGD.
DR GO; GO:0050918; P:positive chemotaxis; ISO:RGD.
DR GO; GO:0032233; P:positive regulation of actin filament bundle assembly; ISO:RGD.
DR GO; GO:0051041; P:positive regulation of calcium-independent cell-cell adhesion; ISO:RGD.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
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; IGI:ARUK-UCL.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISO:RGD.
DR GO; GO:0050729; P:positive regulation of inflammatory response; ISO:RGD.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IMP:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:1904141; P:positive regulation of microglial cell migration; ISO:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IDA:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:ARUK-UCL.
DR GO; GO:0051281; P:positive regulation of release of sequestered calcium ion into cytosol; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:ARUK-UCL.
DR GO; GO:0032914; P:positive regulation of transforming growth factor beta1 production; ISO:RGD.
DR GO; GO:0031664; P:regulation of lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IGI:ARUK-UCL.
DR GO; GO:0042060; P:wound healing; ISO:RGD.
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; 2.
DR PANTHER; PTHR12015:SF92; PTHR12015:SF92; 2.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
PE 2: Evidence at transcript level;
KW Cell adhesion; Cell membrane; Chemotaxis; Cytokine; Disulfide bond;
KW Glycoprotein; Inflammatory response; Membrane; Reference proteome;
KW Secreted; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..393
FT /note="Fractalkine"
FT /id="PRO_0000005254"
FT CHAIN 25..?335
FT /note="Processed fractalkine"
FT /id="PRO_0000296226"
FT TOPO_DOM 25..337
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 338..358
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 359..393
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:0000250|UniProtKB:P78423"
FT REGION 101..337
FT /note="Mucin-like stalk"
FT REGION 114..184
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 148..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..259
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 281..299
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 335..336
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 DISULFID 32..58
FT /evidence="ECO:0000250|UniProtKB:P78423"
FT DISULFID 36..74
FT /evidence="ECO:0000250|UniProtKB:P78423"
SQ SEQUENCE 393 AA; 41977 MW; F06BB027CBD8CE14 CRC64;
MAPSQLAWLL RLAAFFHLCT LLAGQHLGMT KCNITCHKMT SPIPVTLLIH YQLNQESCGK
RAIILETRQH RHFCADPKEK WVQDAMKHLD HQTAALTRNG GKFEKRVDNV TPRITSATRG
LSPTALAKPE SATVEDLTLE PTAISQEARR PMGTSQEPPA AVTGSSPSTS KAQDAGLAAK
PQSTGISEVA AVSTTIWPSS AVYQSGSSLW AEEKATESPP TIALSTQAST TSSPKQNVGS
EGQPPWVQEQ DSTPEKSPGP EETNPVHTDI FQDRGPGSTV HPSVAPTSSE KTPSPELVAS
GSQAPKVEEP IHATADPQKL SVFITPVPDS QAATRRQAVG LLAFLGLLFC LGVAMFAYQS
LQGCPRKMAG EMVEGLRYVP RSCGSNSYVL VPV
