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Protein

CX3C chemokine receptor 1

Gene

CX3CR1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processHost-virus interaction

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000168329.13
HGNCiHGNC:2558 CX3CR1
MIMi601470 gene
neXtProtiNX_P49238

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 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

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

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

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC167Q9P0B64EBI-13049264,EBI-9083477

GO - Molecular functioni

  • C-X3-C chemokine binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107904, 1 interactor
DIPiDIP-5879N
IntActiP49238, 4 interactors
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
OMAiPQFMFTK
OrthoDBiEOG091G0D5U
PhylomeDBiP49238
TreeFamiTF330966

Family and domain databases

CDDicd15186 7tmA_CX3CR1, 1 hit
InterProiView protein in InterPro
IPR005387 Chemokine_CX3CR1
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01562 FRACTALKINER
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 → D1 PublicationCorresponds to variant dbSNP:rs41535248Ensembl.1
Natural variantiVAR_01004157T → A1 PublicationCorresponds to variant dbSNP:rs199811198Ensembl.1
Natural variantiVAR_010042122V → I1 PublicationCorresponds to variant dbSNP:rs143001773Ensembl.1
Natural variantiVAR_022062147V → I. Corresponds to variant dbSNP:rs3732380Ensembl.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 dbSNP:rs3732379Ensembl.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 dbSNP:rs3732378Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiCX3C1_HUMAN
AccessioniPrimary (citable) accession number: P49238
Secondary accession number(s): A0N0N6, B2R5Z4, J3KP17
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: February 28, 2018
This is version 170 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

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health