P78423 (X3CL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

1. Processed fractalkine

Gene names

Name:	CX3CL1
Synonyms:	FKN, NTT, SCYD1
ORF Names:	A-152E5.2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	397 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	The soluble form is chemotactic for T-cells and monocytes, but 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. Binds to CX3CR1. Ref.8
Subunit structure	Monomer. Interacts with pox virus crmD; this inhibits cell migration mediated by CX3CL1. Ref.6 Ref.8
Subcellular location	Cell membrane; Single-pass type I membrane protein. Processed fractalkine: Secreted.
Tissue specificity	Small intestine, colon, testis, prostate, heart, brain, lung, skeletal muscle, kidney and pancreas.
Induction	By TNF and IL1/interleukin-1 in pulmonary endothelial cells and umbilical vein endothelial cells.
Post-translational modification	A soluble short 95 kDa form may be released by proteolytic cleavage from the long membrane-anchored form By similarity. O-glycosylated with core 1 or possibly core 8 glycans. Ref.5
Sequence similarities	Belongs to the intercrine delta family.

Ontologies

Keywords
Biological process	Cell adhesion Chemotaxis
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Cytokine
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis involved in wound healing Inferred from electronic annotation. Source: Compara cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW cytokine-mediated signaling pathway Traceable author statement PubMed 11777952. Source: UniProtKB defense response Traceable author statement PubMed 12714508. Source: UniProtKB immune response Traceable author statement PubMed 12714508. Source: UniProtKB leukocyte adhesive activation Traceable author statement PubMed 12714508. Source: UniProtKB leukocyte chemotaxis Traceable author statement PubMed 11777952. Source: UniProtKB lymphocyte chemotaxis Inferred from electronic annotation. Source: Compara macrophage chemotaxis Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara neutrophil chemotaxis Inferred from electronic annotation. Source: Compara positive regulation of angiogenesis Inferred from electronic annotation. Source: Compara positive regulation of calcium-independent cell-cell adhesion Inferred from direct assay PubMed 12714508. Source: UniProtKB positive regulation of inflammatory response Inferred from expression pattern PubMed 11777952. Source: UniProtKB positive regulation of transforming growth factor beta1 production Inferred from electronic annotation. Source: Compara
Cellular_component	cell surface Inferred from direct assay PubMed 12714508. Source: UniProtKB extracellular region Inferred from direct assay PubMed 12714508. Source: UniProtKB extracellular space Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from direct assay PubMed 12714508. Source: UniProtKB plasma membrane Traceable author statement. Source: Reactome
Molecular_function	chemokine activity Inferred from direct assay Ref.8. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 397

373

Fractalkine

PRO_0000005252

Chain

25 – ?339

315

Processed fractalkine

PRO_0000296224

Regions

Topological domain

25 – 341

317

Extracellular Potential

Transmembrane

342 – 362

21

Helical; Potential

Topological domain

363 – 397

35

Cytoplasmic Potential

Region

25 – 100

76

Chemokine

Region

101 – 341

241

Mucin-like stalk

Sites

Site

339 – 340

2

Cleavage; to produce soluble form Potential

Amino acid modifications

Glycosylation

33

1

N-linked (GlcNAc...) Potential

Glycosylation

183

1

O-linked (GalNAc...) Ref.5

Glycosylation

253

1

O-linked (GalNAc...) Ref.4 Ref.5

Glycosylation

329

1

O-linked (GalNAc...) Ref.4 Ref.5

Disulfide bond

32 ↔ 58

Ref.7

Disulfide bond

36 ↔ 74

Ref.7

Natural variations

Natural variant

240

1

A → V.
Corresponds to variant rs35860084 [ dbSNP | Ensembl ].

VAR_048714

Secondary structure

1

.

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.

.

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.

.

.

.

.

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.

.

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397

Helix Strand Turn

Details...

Beta strand

34 – 36

3

Helix

45 – 47

3

Beta strand

48 – 53

6

Helix

56 – 58

3

Beta strand

59 – 61

3

Beta strand

63 – 67

5

Turn

68 – 70

3

Beta strand

72 – 75

4

Helix

80 – 90

11

Turn

94 – 96

3

Sequences

	Sequence		Length	Mass (Da)
	P78423 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: BAC71F5080DF9CA6	FASTA	397	42,203
	10 20 30 40 50 60 MAPISLSWLL RLATFCHLTV LLAGQHHGVT KCNITCSKMT SKIPVALLIH YQQNQASCGK 70 80 90 100 110 120 RAIILETRQH RLFCADPKEQ WVKDAMQHLD RQAAALTRNG GTFEKQIGEV KPRTTPAAGG 130 140 150 160 170 180 MDESVVLEPE ATGESSSLEP TPSSQEAQRA LGTSPELPTG VTGSSGTRLP PTPKAQDGGP 190 200 210 220 230 240 VGTELFRVPP VSTAATWQSS APHQPGPSLW AEAKTSEAPS TQDPSTQAST ASSPAPEENA 250 260 270 280 290 300 PSEGQRVWGQ GQSPRPENSL EREEMGPVPA HTDAFQDWGP GSMAHVSVVP VSSEGTPSRE 310 320 330 340 350 360 PVASGSWTPK AEEPIHATMD PQRLGVLITP VPDAQAATRR QAVGLLAFLG LLFCLGVAMF 370 380 390 TYQSLQGCPR KMAGEMAEGL RYIPRSCGSN SYVLVPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A new class of membrane-bound chemokine with a CX3C motif." Bazan J.F., Bacon K.B., Hardiman G., Wang W., Soo K., Rossi D., Greaves D.R., Zlotnik A., Schall T.J. Nature 385:640-644(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Enrichment of glycopeptides for glycan structure and attachment site identification." Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G. Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT SER-253 AND THR-329, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY. Tissue: Cerebrospinal fluid.
[5]	"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD." Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G. Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT THR-183; SER-253 AND THR-329, STRUCTURE OF CARBOHYDRATES, MASS SPECTROMETRY.
[6]	"Solution structure and dynamics of the CX3C chemokine domain of fractalkine and its interaction with an N-terminal fragment of CX3CR1." Mizoue L.S., Bazan J.F., Johnson E.C., Handel T.M. Biochemistry 38:1402-1414(1999) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 25-100, SUBUNIT, INTERACTION WITH CX3CR1.
[7]	"The crystal structure of the chemokine domain of fractalkine shows a novel quaternary arrangement." Hoover D.M., Mizoue L.S., Handel T.M., Lubkowski J. J. Biol. Chem. 275:23187-23193(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 25-98, DISULFIDE BONDS.
[8]	"Structural basis of chemokine sequestration by CrmD, a poxvirus-encoded tumor necrosis factor receptor." Xue X., Lu Q., Wei H., Wang D., Chen D., He G., Huang L., Wang H., Wang X. PLoS Pathog. 7:E1002162-E1002162(2011) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 24-100 IN COMPLEX WITH POX VIRUS CRMD, FUNCTION, INTERACTION WITH VIRAL CRMD.
+	Additional computationally mapped references.

Web resources

Wikipedia

CX3CL1 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00019771.

RefSeq

NP_002987.1. NM_002996.3.

UniGene

Hs.531668.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B2T	NMR	-	A	25-100	[»]
1F2L	X-ray	2.00	A/B/C/D	25-98	[»]
3ONA	X-ray	2.60	B	24-100	[»]

ProteinModelPortal

P78423.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5878N.

STRING

9606.ENSP00000006053.

PTM databases

PhosphoSite

P78423.

Polymorphism databases

DMDM

6175080.

Proteomic databases

PaxDb

P78423.

PeptideAtlas

P78423.

PRIDE

P78423.

Protocols and materials databases

DNASU

6376.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000006053; ENSP00000006053; ENSG00000006210.

GeneID

6376.

KEGG

hsa:6376.

UCSC

uc002eli.3. human.

Organism-specific databases

CTD

6376.

GeneCards

GC16P057406.

HGNC

HGNC:10647. CX3CL1.

HPA

CAB026192.
HPA040361.

MIM

601880. gene.

neXtProt

NX_P78423.

PharmGKB

PA35577.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG46337.

HOGENOM

HOG000036946.

HOVERGEN

HBG057269.

InParanoid

P78423.

KO

K05508.

OMA

YQSLQGC.

OrthoDB

EOG415GDN.

PhylomeDB

P78423.

Enzyme and pathway databases

Reactome

REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

P78423.

Bgee

P78423.

CleanEx

HS_CX3CL1.

Genevestigator

P78423.

GermOnline

ENSG00000006210. Homo sapiens.

Family and domain databases

InterPro

IPR008097. Chemokine_CX3CL1.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]

Pfam

PF00048. IL8. 1 hit.
[Graphical view]

PRINTS

PR01721. FRACTALKINE.

SMART

SM00199. SCY. 1 hit.
[Graphical view]

SUPFAM

SSF54117. Chemokine_IL8. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P78423.

GenomeRNAi

6376.

NextBio

24772.

PMAP-CutDB

P78423.

SOURCE

Search...

Entry information

Entry name

X3CL1_HUMAN

Accession

Primary (citable) accession number: P78423
Secondary accession number(s): O00672

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 1997
Last modified:	May 1, 2013
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.