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Protein

Fractalkine

Gene

CX3CL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • chemoattractant activity Source: ARUK-UCL
  • chemokine activity Source: UniProtKB
  • CX3C chemokine receptor binding Source: UniProtKB
  • CXCR1 chemokine receptor binding Source: ARUK-UCL
  • integrin binding Source: UniProtKB
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionCytokine
Biological processCell adhesion, Chemotaxis

Enzyme and pathway databases

ReactomeiR-HSA-380108 Chemokine receptors bind chemokines
R-HSA-418594 G alpha (i) signalling events
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

EuPathDBiHostDB:ENSG00000006210.6
HGNCiHGNC:10647 CX3CL1
MIMi601880 gene
neXtProtiNX_P78423

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Disulfide bondi36 ↔ 741 Publication
Glycosylationi183O-linked (GalNAc...) threonine1 Publication1
Glycosylationi253O-linked (GalNAc...) serine2 Publications1
Glycosylationi329O-linked (GalNAc...) threonine2 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
ProteomicsDBi57622

PTM databases

GlyConnecti698
iPTMnetiP78423
PhosphoSitePlusiP78423
UniCarbKBiP78423

Miscellaneous databases

PMAP-CutDBiP78423

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 Expressed in 200 organ(s), highest expression level in thoracic mammary gland
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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112278, 2 interactors
DIPiDIP-5878N
IntActiP78423, 13 interactors
STRINGi9606.ENSP00000006053

Structurei

Secondary structure

1397
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

CDDicd00274 Chemokine_CX3C, 1 hit
InterProiView protein in InterPro
IPR039809 Chemokine_b/g/d
IPR034127 Chemokine_CX3C
IPR001811 Chemokine_IL8-like_dom
IPR008097 CX3CL1
IPR036048 Interleukin_8-like_sf
PANTHERiPTHR12015 PTHR12015, 1 hit
PTHR12015:SF92 PTHR12015:SF92, 1 hit
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BSR6H3BSR6_HUMAN
Fractalkine
CX3CL1
403Annotation score:
J3QRA1J3QRA1_HUMAN
Fractalkine
CX3CL1
359Annotation score:
H3BV86H3BV86_HUMAN
Fractalkine
CX3CL1
55Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048714240A → V. Corresponds to variant dbSNP:rs35860084Ensembl.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_002987.1, NM_002996.4
UniGeneiHs.531668

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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_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
IntActiP78423, 13 interactors
STRINGi9606.ENSP00000006053

PTM databases

GlyConnecti698
iPTMnetiP78423
PhosphoSitePlusiP78423
UniCarbKBiP78423

Polymorphism and mutation databases

BioMutaiCX3CL1
DMDMi6175080

Proteomic databases

PaxDbiP78423
PeptideAtlasiP78423
PRIDEiP78423
ProteomicsDBi57622

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
EuPathDBiHostDB:ENSG00000006210.6
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

ReactomeiR-HSA-380108 Chemokine receptors bind chemokines
R-HSA-418594 G alpha (i) signalling events
SIGNORiP78423

Miscellaneous databases

EvolutionaryTraceiP78423
GeneWikiiCX3CL1
GenomeRNAii6376
PMAP-CutDBiP78423
PROiPR:P78423
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000006210 Expressed in 200 organ(s), highest expression level in thoracic mammary gland
CleanExiHS_CX3CL1
ExpressionAtlasiP78423 baseline and differential
GenevisibleiP78423 HS

Family and domain databases

CDDicd00274 Chemokine_CX3C, 1 hit
InterProiView protein in InterPro
IPR039809 Chemokine_b/g/d
IPR034127 Chemokine_CX3C
IPR001811 Chemokine_IL8-like_dom
IPR008097 CX3CL1
IPR036048 Interleukin_8-like_sf
PANTHERiPTHR12015 PTHR12015, 1 hit
PTHR12015:SF92 PTHR12015:SF92, 1 hit
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiX3CL1_HUMAN
AccessioniPrimary (citable) accession number: P78423
Secondary accession number(s): O00672
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: May 1, 1997
Last modified: November 7, 2018
This is version 173 of the entry and version 1 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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