Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

CX3C chemokine receptor 1

Gene

CX3CR1

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

Functioni

Receptor for the CX3C chemokine fractalkine (CX3CL1); binds to CX3CL1 and mediates both its adhesive and migratory functions (PubMed:9390561, PubMed:23125415). Acts as coreceptor with CD4 for HIV-1 virus envelope protein (in vitro) (PubMed:9726990). Isoform 2 and isoform 3 seem to be more potent HIV-1 coreceptors than isoform 1 (PubMed:14607932).4 Publications

GO - Molecular functioni

  • chemokine receptor activity Source: ProtInc
  • C-X3-C chemokine binding Source: UniProtKB
  • C-X3-C chemokine receptor activity Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Host-virus interaction

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168329-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
SIGNORiP49238.

Names & Taxonomyi

Protein namesi
Recommended name:
CX3C chemokine receptor 1
Short name:
C-X3-C CKR-1
Short name:
CX3CR1
Alternative name(s):
Beta chemokine receptor-like 1
CMK-BRL-1
Short name:
CMK-BRL1
Fractalkine receptor
G-protein coupled receptor 13
V28
Gene namesi
Name:CX3CR1
Synonyms:CMKBRL1, GPR13
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:2558. CX3CR1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 31ExtracellularSequence analysisAdd BLAST31
Transmembranei32 – 59Helical; Name=1Sequence analysisAdd BLAST28
Topological domaini60 – 69CytoplasmicSequence analysis10
Transmembranei70 – 90Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini91 – 103ExtracellularSequence analysisAdd BLAST13
Transmembranei104 – 125Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini126 – 142CytoplasmicSequence analysisAdd BLAST17
Transmembranei143 – 167Helical; Name=4Sequence analysisAdd BLAST25
Topological domaini168 – 195ExtracellularSequence analysisAdd BLAST28
Transmembranei196 – 215Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini216 – 231CytoplasmicSequence analysisAdd BLAST16
Transmembranei232 – 256Helical; Name=6Sequence analysisAdd BLAST25
Topological domaini257 – 273ExtracellularSequence analysisAdd BLAST17
Transmembranei274 – 297Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini298 – 355CytoplasmicSequence analysisAdd BLAST58

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Macular degeneration, age-related, 12 (ARMD12)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
See also OMIM:613784
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_010043249V → I Common polymorphism in Caucasian population; associated with a markedly reduced risk of acute coronary artery disease; associated with higher risk of developing ARMD12; chemotaxis of monocytes of individuals with homozygous Ile-249 and Met-280 genotypes is impaired in the presence of bound CX3CR1 protein. 6 PublicationsCorresponds to variant rs3732379dbSNPEnsembl.1
Natural variantiVAR_010044280T → M Common polymorphism in Caucasian population; associated with higher risk of developing ARMD12; chemotaxis of monocytes of individuals with homozygous Met-280 and Ile-249 genotypes is impaired in the presence of bound CX3CR1 protein. 5 PublicationsCorresponds to variant rs3732378dbSNPEnsembl.1

Keywords - Diseasei

Age-related macular degeneration

Organism-specific databases

DisGeNETi1524.
MalaCardsiCX3CR1.
MIMi609423. phenotype.
613784. phenotype.
OpenTargetsiENSG00000168329.
Orphaneti279. Age-related macular degeneration.
PharmGKBiPA27054.

Chemistry databases

ChEMBLiCHEMBL4843.
GuidetoPHARMACOLOGYi74.

Polymorphism and mutation databases

BioMutaiCX3CR1.
DMDMi1351394.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693261 – 355CX3C chemokine receptor 1Add BLAST355

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi102 ↔ 175PROSITE-ProRule annotation
Modified residuei346PhosphothreonineBy similarity1

Post-translational modificationi

This protein is not N-glycosylated which is unusual for G-protein-coupled receptors.By similarity

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiP49238.
PeptideAtlasiP49238.
PRIDEiP49238.

PTM databases

iPTMnetiP49238.
PhosphoSitePlusiP49238.

Expressioni

Tissue specificityi

Expressed in lymphoid and neural tissues.

Gene expression databases

BgeeiENSG00000168329.
CleanExiHS_CX3CR1.
ExpressionAtlasiP49238. baseline and differential.
GenevisibleiP49238. HS.

Organism-specific databases

HPAiCAB032478.
HPA046587.

Interactioni

Subunit structurei

Interacts with human respiratory syncytial virus (HRSV) protein G; this interaction modulates host immune response. Interacts with HIV-1 envelope polyprotein gp160. Found in a ternary complex with CX3CL1 and ITGAV:ITGB3 or ITGA4:ITGB1 (PubMed:23125415).2 Publications

GO - Molecular functioni

  • C-X3-C chemokine binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107904. 1 interactor.
DIPiDIP-5879N.
MINTiMINT-6631119.
STRINGi9606.ENSP00000351059.

Chemistry databases

BindingDBiP49238.

Structurei

3D structure databases

ProteinModelPortaliP49238.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGZ8. Eukaryota.
ENOG41118PP. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP49238.
KOiK04192.
OMAiLPFWTHY.
OrthoDBiEOG091G0D5U.
PhylomeDBiP49238.
TreeFamiTF330966.

Family and domain databases

InterProiIPR005387. Chemokine_CX3CR1.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01562. FRACTALKINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P49238-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL
60 70 80 90 100
LVVFALTNSK KPKSVTDIYL LNLALSDLLF VATLPFWTHY LINEKGLHNA
110 120 130 140 150
MCKFTTAFFF IGFFGSIFFI TVISIDRYLA IVLAANSMNN RTVQHGVTIS
160 170 180 190 200
LGVWAAAILV AAPQFMFTKQ KENECLGDYP EVLQEIWPVL RNVETNFLGF
210 220 230 240 250
LLPLLIMSYC YFRIIQTLFS CKNHKKAKAI KLILLVVIVF FLFWTPYNVM
260 270 280 290 300
IFLETLKLYD FFPSCDMRKD LRLALSVTET VAFSHCCLNP LIYAFAGEKF
310 320 330 340 350
RRYLYHLYGK CLAVLCGRSV HVDFSSSESQ RSRHGSVLSS NFTYHTSDGD

ALLLL
Length:355
Mass (Da):40,396
Last modified:February 1, 1996 - v1
Checksum:iC59DC5F4C4312F22
GO
Isoform 2 (identifier: P49238-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MREPLEALKLADLDFRKSSLASGWRMASGAFTM

Show »
Length:387
Mass (Da):43,935
Checksum:i446834BF5BF0FC5B
GO
Isoform 3 (identifier: P49238-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MASGAFTM

Show »
Length:362
Mass (Da):41,062
Checksum:i193A12DC884FC41B
GO
Isoform 4 (identifier: P49238-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MREPLEAFKLADLDFRKSSLASGWRMASGAFTM

Note: No experimental confirmation available.Curated
Show »
Length:387
Mass (Da):43,969
Checksum:iA90DFBDE74941C59
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 4 (identifier: P49238-4)
Sequence conflicti8F → L in DA413545 (PubMed:14702039).Curated1

Polymorphismi

Variations in CX3CR1 are associated with rapid progression to AIDS [MIMi:609423]. Increased susceptibility to HIV infection and rapid progression to AIDS are associated with the Ile-249/Met-280 haplotype.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04938613E → D.1 PublicationCorresponds to variant rs41535248dbSNPEnsembl.1
Natural variantiVAR_01004157T → A.1 PublicationCorresponds to variant rs199811198dbSNPEnsembl.1
Natural variantiVAR_010042122V → I.1 PublicationCorresponds to variant rs143001773dbSNPEnsembl.1
Natural variantiVAR_022062147V → I.Corresponds to variant rs3732380dbSNPEnsembl.1
Natural variantiVAR_010043249V → I Common polymorphism in Caucasian population; associated with a markedly reduced risk of acute coronary artery disease; associated with higher risk of developing ARMD12; chemotaxis of monocytes of individuals with homozygous Ile-249 and Met-280 genotypes is impaired in the presence of bound CX3CR1 protein. 6 PublicationsCorresponds to variant rs3732379dbSNPEnsembl.1
Natural variantiVAR_010044280T → M Common polymorphism in Caucasian population; associated with higher risk of developing ARMD12; chemotaxis of monocytes of individuals with homozygous Met-280 and Ile-249 genotypes is impaired in the presence of bound CX3CR1 protein. 5 PublicationsCorresponds to variant rs3732378dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0096811M → MREPLEALKLADLDFRKSSL ASGWRMASGAFTM in isoform 2. Curated1
Alternative sequenceiVSP_0096821M → MASGAFTM in isoform 3. Curated1
Alternative sequenceiVSP_0445951M → MREPLEAFKLADLDFRKSSL ASGWRMASGAFTM in isoform 4. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20350 mRNA. Translation: AAA91783.1.
U28934 mRNA. Translation: AAA87032.1.
AY016370 Genomic DNA. Translation: AAK08627.1.
AK312373 mRNA. Translation: BAG35291.1.
DA413545 mRNA. No translation available.
EF064744 Genomic DNA. Translation: ABK41927.1.
EU006531 Genomic DNA. Translation: ABS29268.1.
AC092053 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64576.1.
BC028078 mRNA. Translation: AAH28078.1.
CCDSiCCDS43069.1. [P49238-1]
CCDS54571.1. [P49238-4]
PIRiJC4304.
RefSeqiNP_001164642.1. NM_001171171.1. [P49238-1]
NP_001164643.1. NM_001171172.1. [P49238-1]
NP_001164645.1. NM_001171174.1. [P49238-4]
NP_001328.1. NM_001337.3. [P49238-1]
UniGeneiHs.78913.

Genome annotation databases

EnsembliENST00000358309; ENSP00000351059; ENSG00000168329. [P49238-4]
ENST00000399220; ENSP00000382166; ENSG00000168329. [P49238-1]
ENST00000541347; ENSP00000439140; ENSG00000168329. [P49238-1]
ENST00000542107; ENSP00000444928; ENSG00000168329. [P49238-1]
GeneIDi1524.
KEGGihsa:1524.
UCSCiuc003cjl.4. human. [P49238-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20350 mRNA. Translation: AAA91783.1.
U28934 mRNA. Translation: AAA87032.1.
AY016370 Genomic DNA. Translation: AAK08627.1.
AK312373 mRNA. Translation: BAG35291.1.
DA413545 mRNA. No translation available.
EF064744 Genomic DNA. Translation: ABK41927.1.
EU006531 Genomic DNA. Translation: ABS29268.1.
AC092053 Genomic DNA. No translation available.
CH471055 Genomic DNA. Translation: EAW64576.1.
BC028078 mRNA. Translation: AAH28078.1.
CCDSiCCDS43069.1. [P49238-1]
CCDS54571.1. [P49238-4]
PIRiJC4304.
RefSeqiNP_001164642.1. NM_001171171.1. [P49238-1]
NP_001164643.1. NM_001171172.1. [P49238-1]
NP_001164645.1. NM_001171174.1. [P49238-4]
NP_001328.1. NM_001337.3. [P49238-1]
UniGeneiHs.78913.

3D structure databases

ProteinModelPortaliP49238.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107904. 1 interactor.
DIPiDIP-5879N.
MINTiMINT-6631119.
STRINGi9606.ENSP00000351059.

Chemistry databases

BindingDBiP49238.
ChEMBLiCHEMBL4843.
GuidetoPHARMACOLOGYi74.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP49238.
PhosphoSitePlusiP49238.

Polymorphism and mutation databases

BioMutaiCX3CR1.
DMDMi1351394.

Proteomic databases

PaxDbiP49238.
PeptideAtlasiP49238.
PRIDEiP49238.

Protocols and materials databases

DNASUi1524.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000358309; ENSP00000351059; ENSG00000168329. [P49238-4]
ENST00000399220; ENSP00000382166; ENSG00000168329. [P49238-1]
ENST00000541347; ENSP00000439140; ENSG00000168329. [P49238-1]
ENST00000542107; ENSP00000444928; ENSG00000168329. [P49238-1]
GeneIDi1524.
KEGGihsa:1524.
UCSCiuc003cjl.4. human. [P49238-1]

Organism-specific databases

CTDi1524.
DisGeNETi1524.
GeneCardsiCX3CR1.
HGNCiHGNC:2558. CX3CR1.
HPAiCAB032478.
HPA046587.
MalaCardsiCX3CR1.
MIMi601470. gene.
609423. phenotype.
613784. phenotype.
neXtProtiNX_P49238.
OpenTargetsiENSG00000168329.
Orphaneti279. Age-related macular degeneration.
PharmGKBiPA27054.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGZ8. Eukaryota.
ENOG41118PP. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP49238.
KOiK04192.
OMAiLPFWTHY.
OrthoDBiEOG091G0D5U.
PhylomeDBiP49238.
TreeFamiTF330966.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000168329-MONOMER.
ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
SIGNORiP49238.

Miscellaneous databases

GeneWikiiCX3CR1.
GenomeRNAii1524.
PROiP49238.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168329.
CleanExiHS_CX3CR1.
ExpressionAtlasiP49238. baseline and differential.
GenevisibleiP49238. HS.

Family and domain databases

InterProiIPR005387. Chemokine_CX3CR1.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01562. FRACTALKINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCX3C1_HUMAN
AccessioniPrimary (citable) accession number: P49238
Secondary accession number(s): A0N0N6, B2R5Z4, J3KP17
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: November 2, 2016
This is version 162 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

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 3
    Human chromosome 3: 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. 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.