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Protein

Fractalkine

Gene

CX3CL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a ligand for both CX3CR1 and integrins. Binds to CX3CR1 (PubMed:23125415, PubMed:9931005, PubMed:21829356). Binds to integrins ITGAV:ITGB3 and ITGA4:ITGB1. Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner. In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins. In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 (PubMed:23125415, PubMed:24789099). The soluble form is chemotactic for T-cells and monocytes and not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium (PubMed:9024663, PubMed:9177350).6 Publications

GO - Molecular functioni

  • CCR chemokine receptor binding Source: GO_Central
  • chemokine activity Source: UniProtKB
  • CX3C chemokine receptor binding Source: UniProtKB
  • integrin binding Source: UniProtKB
  • receptor binding Source: UniProtKB

GO - Biological processi

  • angiogenesis involved in wound healing Source: Ensembl
  • cell adhesion Source: UniProtKB-KW
  • cellular response to interferon-gamma Source: GO_Central
  • cellular response to interleukin-1 Source: GO_Central
  • cellular response to tumor necrosis factor Source: GO_Central
  • chemokine-mediated signaling pathway Source: GO_Central
  • chemotaxis Source: UniProtKB
  • cytokine-mediated signaling pathway Source: UniProtKB
  • defense response Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: GO_Central
  • immune response Source: UniProtKB
  • integrin activation Source: UniProtKB
  • leukocyte adhesive activation Source: UniProtKB
  • leukocyte chemotaxis Source: UniProtKB
  • leukocyte migration involved in inflammatory response Source: UniProtKB
  • lymphocyte chemotaxis Source: GO_Central
  • monocyte chemotaxis Source: GO_Central
  • negative regulation of cell migration Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • neutrophil chemotaxis Source: GO_Central
  • positive regulation of angiogenesis Source: Ensembl
  • positive regulation of calcium-independent cell-cell adhesion Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: GO_Central
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of inflammatory response Source: UniProtKB
  • positive regulation of transforming growth factor beta1 production Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Cell adhesion, Chemotaxis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006210-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
SIGNORiP78423.

Names & Taxonomyi

Protein namesi
Recommended name:
Fractalkine
Alternative name(s):
C-X3-C motif chemokine 1
CX3C membrane-anchored chemokine
Neurotactin
Small-inducible cytokine D1
Cleaved into the following chain:
Gene namesi
Name:CX3CL1
Synonyms:FKN, NTT, SCYD1
ORF Names:A-152E5.2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:10647. CX3CL1.

Subcellular locationi

Processed fractalkine :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini25 – 341ExtracellularSequence analysisAdd BLAST317
Transmembranei342 – 362HelicalSequence analysisAdd BLAST21
Topological domaini363 – 397CytoplasmicSequence analysisAdd BLAST35

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
  • integral component of membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi60K → A: Reduced binding to integrin ITGAV:ITGB3, but no effect on binding to CX3CR1; when associated with A-61. 1 Publication1
Mutagenesisi60K → E: Dominant-negative mutant, reduced binding to integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding to CX3CR1, defective in ternary complex formation, integrin activation and fractalkine signaling and suppression of leukocyte recruitment in the peritonitis model in vivo; when associated with E-61. 2 Publications1
Mutagenesisi61R → A: Reduced binding to integrin ITGAV:ITGB3, but no effect on binding to CX3CR1; when associated with A-60. 1 Publication1
Mutagenesisi61R → E: Dominant-negative mutant, reduced binding to integrins ITGAV:ITGB3 and ITGA4:ITGB1, no effect on binding to CX3CR1, defective in ternary complex formation, integrin activation and fractalkine signaling and suppression of leukocyte recruitment in the peritonitis model in vivo; when associated with E-60. 2 Publications1
Mutagenesisi71R → A: Loss of binding to CX3CR1 and ability to induce chemotaxis but no effect on binding to integrins. 1 Publication1
Mutagenesisi78K → A: Little or no effect on binding to integrin ITGAV:ITGB3. 1 Publication1
Mutagenesisi78K → A: Little or no effect on binding to integrin ITGAV:ITGB3; when associated with A-83. 1 Publication1
Mutagenesisi83K → A: Little or no effect on binding to integrin ITGAV:ITGB3; when associated with A-78. 1 Publication1

Organism-specific databases

DisGeNETi6376.
OpenTargetsiENSG00000006210.
PharmGKBiPA35577.

Polymorphism and mutation databases

BioMutaiCX3CL1.
DMDMi6175080.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 24Add BLAST24
ChainiPRO_000000525225 – 397FractalkineAdd BLAST373
ChainiPRO_000029622425 – ?339Processed fractalkineAdd BLAST315

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi32 ↔ 581 Publication
Glycosylationi33N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi36 ↔ 741 Publication
Glycosylationi183O-linked (GalNAc...)1 Publication1
Glycosylationi253O-linked (GalNAc...)2 Publications1
Glycosylationi329O-linked (GalNAc...)2 Publications1

Post-translational modificationi

A soluble short 95 kDa form may be released by proteolytic cleavage from the long membrane-anchored form.1 Publication
O-glycosylated with core 1 or possibly core 8 glycans.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei339 – 340Cleavage; to produce soluble formSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP78423.
PeptideAtlasiP78423.
PRIDEiP78423.

PTM databases

iPTMnetiP78423.
PhosphoSitePlusiP78423.
UniCarbKBiP78423.

Miscellaneous databases

PMAP-CutDBP78423.

Expressioni

Tissue specificityi

Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level). Small intestine, colon, testis, prostate, heart, brain, lung, skeletal muscle, kidney and pancreas. Most abundant in the brain and heart.3 Publications

Inductioni

By TNF and IL1/interleukin-1 in pulmonary endothelial cells and umbilical vein endothelial cells.1 Publication

Gene expression databases

BgeeiENSG00000006210.
CleanExiHS_CX3CL1.
ExpressionAtlasiP78423. baseline and differential.
GenevisibleiP78423. HS.

Organism-specific databases

HPAiCAB026192.
HPA040361.

Interactioni

Subunit structurei

Monomer (PubMed:9931005). Interacts with pox virus crmD; this inhibits cell migration mediated by CX3CL1 (PubMed:21829356). Forms a ternary complex with CX3CR1 and ITGAV:ITGB3 or ITGA4:ITGB1 (PubMed:23125415).3 Publications

GO - Molecular functioni

  • CCR chemokine receptor binding Source: GO_Central
  • chemokine activity Source: UniProtKB
  • CX3C chemokine receptor binding Source: UniProtKB
  • integrin binding Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112278. 2 interactors.
DIPiDIP-5878N.
STRINGi9606.ENSP00000006053.

Structurei

Secondary structure

1397
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 36Combined sources3
Helixi45 – 47Combined sources3
Beta strandi48 – 53Combined sources6
Helixi56 – 58Combined sources3
Beta strandi59 – 61Combined sources3
Beta strandi63 – 67Combined sources5
Turni68 – 70Combined sources3
Beta strandi72 – 75Combined sources4
Helixi80 – 90Combined sources11
Helixi93 – 96Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B2TNMR-A25-100[»]
1F2LX-ray2.00A/B/C/D25-98[»]
3ONAX-ray2.60B24-100[»]
4XT1X-ray2.89B26-101[»]
4XT3X-ray3.80B26-101[»]
ProteinModelPortaliP78423.
SMRiP78423.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP78423.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni25 – 100Chemokine and involved in interaction with ITGAV:ITGB3 and ITGA4:ITGB11 PublicationAdd BLAST76
Regioni101 – 341Mucin-like stalkAdd BLAST241

Sequence similaritiesi

Belongs to the intercrine delta family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IJQZ. Eukaryota.
ENOG41116BY. LUCA.
GeneTreeiENSGT00510000049483.
HOGENOMiHOG000036946.
HOVERGENiHBG057269.
InParanoidiP78423.
KOiK05508.
PhylomeDBiP78423.
TreeFamiTF337534.

Family and domain databases

InterProiIPR001811. Chemokine_IL8-like_dom.
IPR008097. CX3CL1.
[Graphical view]
PANTHERiPTHR12015:SF92. PTHR12015:SF92. 1 hit.
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P78423-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAPISLSWLL RLATFCHLTV LLAGQHHGVT KCNITCSKMT SKIPVALLIH
60 70 80 90 100
YQQNQASCGK RAIILETRQH RLFCADPKEQ WVKDAMQHLD RQAAALTRNG
110 120 130 140 150
GTFEKQIGEV KPRTTPAAGG MDESVVLEPE ATGESSSLEP TPSSQEAQRA
160 170 180 190 200
LGTSPELPTG VTGSSGTRLP PTPKAQDGGP VGTELFRVPP VSTAATWQSS
210 220 230 240 250
APHQPGPSLW AEAKTSEAPS TQDPSTQAST ASSPAPEENA PSEGQRVWGQ
260 270 280 290 300
GQSPRPENSL EREEMGPVPA HTDAFQDWGP GSMAHVSVVP VSSEGTPSRE
310 320 330 340 350
PVASGSWTPK AEEPIHATMD PQRLGVLITP VPDAQAATRR QAVGLLAFLG
360 370 380 390
LLFCLGVAMF TYQSLQGCPR KMAGEMAEGL RYIPRSCGSN SYVLVPV
Length:397
Mass (Da):42,203
Last modified:May 1, 1997 - v1
Checksum:iBAC71F5080DF9CA6
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048714240A → V.Corresponds to variant rs35860084dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U91835 mRNA. Translation: AAB50014.1.
U84487 mRNA. Translation: AAB49679.1.
AC004382 Genomic DNA. Translation: AAC24307.1.
BC001163 mRNA. Translation: AAH01163.1.
BC016164 mRNA. Translation: AAH16164.1.
CCDSiCCDS10779.1.
RefSeqiNP_001291321.1. NM_001304392.1.
NP_002987.1. NM_002996.4.
UniGeneiHs.531668.

Genome annotation databases

EnsembliENST00000006053; ENSP00000006053; ENSG00000006210.
GeneIDi6376.
KEGGihsa:6376.
UCSCiuc002eli.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

CX3CL1 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U91835 mRNA. Translation: AAB50014.1.
U84487 mRNA. Translation: AAB49679.1.
AC004382 Genomic DNA. Translation: AAC24307.1.
BC001163 mRNA. Translation: AAH01163.1.
BC016164 mRNA. Translation: AAH16164.1.
CCDSiCCDS10779.1.
RefSeqiNP_001291321.1. NM_001304392.1.
NP_002987.1. NM_002996.4.
UniGeneiHs.531668.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B2TNMR-A25-100[»]
1F2LX-ray2.00A/B/C/D25-98[»]
3ONAX-ray2.60B24-100[»]
4XT1X-ray2.89B26-101[»]
4XT3X-ray3.80B26-101[»]
ProteinModelPortaliP78423.
SMRiP78423.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112278. 2 interactors.
DIPiDIP-5878N.
STRINGi9606.ENSP00000006053.

PTM databases

iPTMnetiP78423.
PhosphoSitePlusiP78423.
UniCarbKBiP78423.

Polymorphism and mutation databases

BioMutaiCX3CL1.
DMDMi6175080.

Proteomic databases

PaxDbiP78423.
PeptideAtlasiP78423.
PRIDEiP78423.

Protocols and materials databases

DNASUi6376.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000006053; ENSP00000006053; ENSG00000006210.
GeneIDi6376.
KEGGihsa:6376.
UCSCiuc002eli.4. human.

Organism-specific databases

CTDi6376.
DisGeNETi6376.
GeneCardsiCX3CL1.
HGNCiHGNC:10647. CX3CL1.
HPAiCAB026192.
HPA040361.
MIMi601880. gene.
neXtProtiNX_P78423.
OpenTargetsiENSG00000006210.
PharmGKBiPA35577.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJQZ. Eukaryota.
ENOG41116BY. LUCA.
GeneTreeiENSGT00510000049483.
HOGENOMiHOG000036946.
HOVERGENiHBG057269.
InParanoidiP78423.
KOiK05508.
PhylomeDBiP78423.
TreeFamiTF337534.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000006210-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
SIGNORiP78423.

Miscellaneous databases

EvolutionaryTraceiP78423.
GeneWikiiCX3CL1.
GenomeRNAii6376.
PMAP-CutDBP78423.
PROiP78423.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006210.
CleanExiHS_CX3CL1.
ExpressionAtlasiP78423. baseline and differential.
GenevisibleiP78423. HS.

Family and domain databases

InterProiIPR001811. Chemokine_IL8-like_dom.
IPR008097. CX3CL1.
[Graphical view]
PANTHERiPTHR12015:SF92. PTHR12015:SF92. 1 hit.
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiX3CL1_HUMAN
AccessioniPrimary (citable) accession number: P78423
Secondary accession number(s): O00672
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: November 30, 2016
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.