P49238 (CX3C1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 126.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 names |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 355 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Receptor for the CX3C chemokine fractalkine and mediates both its adhesive and migratory functions. Acts as coreceptor with CD4 for HIV-1 virus envelope protein (in vitro). Isoform 2 and isoform 3 seem to be more potent HIV-1 coreceptors than isoform 1. |
| Subunit structure | Interacts with human respiratory syncytial virus (HRSV) protein G; this interaction modulates host immune response. Interacts with HIV-1 envelope polyprotein gp160. Ref.10 |
| Subcellular location | |
| Tissue specificity | Expressed in lymphoid and neural tissues. |
| Polymorphism | Variations in CX3CR1 are associated with rapid progression to AIDS [MIM:609423]. Increased susceptibility to HIV infection and rapid progression to AIDS are associated with the Ile-249/Met-280 haplotype. |
| Involvement in disease | Age-related macular degeneration 12 (ARMD12) [MIM:613784]: A 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. |
| Sequence similarities | Belongs to the G-protein coupled receptor 1 family. |
Ontologies
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P49238-1) 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. | ||||||
| Isoform 2 (identifier: P49238-2) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MREPLEALKLADLDFRKSSLASGWRMASGAFTM | ||||||
| Isoform 3 (identifier: P49238-3) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MASGAFTM | ||||||
| Isoform 4 (identifier: P49238-4) The sequence of this isoform differs from the canonical sequence as follows: 1-1: M → MREPLEAFKLADLDFRKSSLASGWRMASGAFTM | ||||||
| Note: No experimental confirmation available. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 355 | 355 | CX3C chemokine receptor 1 | PRO_0000069326 | |||||||
Regions | |||||||||||
| Topological domain | 1 – 31 | 31 | Extracellular Potential | ||||||||
| Transmembrane | 32 – 59 | 28 | Helical; Name=1; Potential | ||||||||
| Topological domain | 60 – 69 | 10 | Cytoplasmic Potential | ||||||||
| Transmembrane | 70 – 90 | 21 | Helical; Name=2; Potential | ||||||||
| Topological domain | 91 – 103 | 13 | Extracellular Potential | ||||||||
| Transmembrane | 104 – 125 | 22 | Helical; Name=3; Potential | ||||||||
| Topological domain | 126 – 142 | 17 | Cytoplasmic Potential | ||||||||
| Transmembrane | 143 – 167 | 25 | Helical; Name=4; Potential | ||||||||
| Topological domain | 168 – 195 | 28 | Extracellular Potential | ||||||||
| Transmembrane | 196 – 215 | 20 | Helical; Name=5; Potential | ||||||||
| Topological domain | 216 – 231 | 16 | Cytoplasmic Potential | ||||||||
| Transmembrane | 232 – 256 | 25 | Helical; Name=6; Potential | ||||||||
| Topological domain | 257 – 273 | 17 | Extracellular Potential | ||||||||
| Transmembrane | 274 – 297 | 24 | Helical; Name=7; Potential | ||||||||
| Topological domain | 298 – 355 | 58 | Cytoplasmic Potential | ||||||||
Amino acid modifications | |||||||||||
| Disulfide bond | 102 ↔ 175 | By similarity | |||||||||
Natural variations | |||||||||||
| Alternative sequence | 1 | 1 | M → MREPLEALKLADLDFRKSSL ASGWRMASGAFTM in isoform 2. | VSP_009681 | |||||||
| Alternative sequence | 1 | 1 | M → MASGAFTM in isoform 3. | VSP_009682 | |||||||
| Alternative sequence | 1 | 1 | M → MREPLEAFKLADLDFRKSSL ASGWRMASGAFTM in isoform 4. | VSP_044595 | |||||||
| Natural variant | 13 | 1 | E → D. Ref.6 Corresponds to variant rs41535248 [ dbSNP | Ensembl ]. | VAR_049386 | |||||||
| Natural variant | 57 | 1 | T → A. Ref.14 | VAR_010041 | |||||||
| Natural variant | 122 | 1 | V → I. Ref.14 | VAR_010042 | |||||||
| Natural variant | 147 | 1 | V → I. Corresponds to variant rs3732380 [ dbSNP | Ensembl ]. | VAR_022062 | |||||||
| Natural variant | 249 | 1 | V → 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. Ref.4 Ref.6 Ref.14 Ref.15 Ref.16 Ref.17 Corresponds to variant rs3732379 [ dbSNP | Ensembl ]. | VAR_010043 | |||||||
| Natural variant | 280 | 1 | T → 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. Ref.4 Ref.6 Ref.14 Ref.16 Ref.17 Corresponds to variant rs3732378 [ dbSNP | Ensembl ]. | VAR_010044 | |||||||
Experimental info | |||||||||||
| Isoform 4: | |||||||||||
| Sequence conflict | 8 | 1 | F → L in DA413545. Ref.4 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "The orphan G-protein-coupled receptor-encoding gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tissues." Raport C.J., Schweickart V.L., Eddy R.L. Jr., Shows T.B., Gray P.W. Gene 163:295-299(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [2] | "Cloning, chromosomal localization, and RNA expression of a human beta chemokine receptor-like gene." Combadiere C., Ahuja S.K., Murphy P.M. DNA Cell Biol. 14:673-680(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | "Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor locus." DeVries M.E., Cao H., Wang J., Xu L., Kelvin A.A., Ran L., Chau L.A., Madrenas J., Hegele R.A., Kelvin D.J. J. Biol. Chem. 278:11985-11994(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [4] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 8-185 (ISOFORM 4), VARIANTS ILE-249 AND MET-280. Tissue: Amygdala and Thalamus. |
| [5] | Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B., Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O., Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I., Nickerson D.A. Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. |
| [6] | NIEHS SNPs program Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-13; ILE-249 AND MET-280. |
| [7] | "The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. Gibbs R.A.Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [9] | "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] (ISOFORM 1). Tissue: Blood. |
| [10] | "CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein." Tripp R.A., Jones L.P., Haynes L.M., Zheng H., Murphy P.M., Anderson L.J. Nat. Immunol. 2:732-738(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HRSV PROTEIN G. |
| [11] | "Two novel fully functional isoforms of CX3CR1 are potent HIV coreceptors." Garin A., Tarantino N., Faure S., Daoudi M., Lecureuil C., Bourdais A., Debre P., Deterre P., Combadiere C. J. Immunol. 171:5305-5312(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, CHARACTERIZATION (ISOFORMS 2 AND 3). |
| [12] | "Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion." Imai T., Hieshima K., Haskell C., Baba M., Nagira M., Nishimura M., Kakizaki M., Takagi S., Nomiyama H., Schall T.J., Yoshie O. Cell 91:521-530(1997) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. |
| [13] | "Identification of CX3CR1. A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1." Combadiere C., Salzwedel K., Smith E.D., Tiffany H.L., Berger E.A., Murphy P.M. J. Biol. Chem. 273:23799-23804(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION. |
| [14] | "Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1." Faure S., Meyer L., Costagliola D., Vaneensberghe C., Genin E., Autran B., Delfraissy J.-F., McDermott D.H., Murphy P.M., Debre P., Theodorou I., Combadiere C. Science 287:2274-2277(2000) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ALA-57; ILE-122; ILE-249 AND MET-280. |
| [15] | "Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease." Moatti D., Faure S., Fumeron F., Amara M.E.-W., Seknadji P., McDermott D.H., Debre P., Aumont M.C., Murphy P.M., de Prost D., Combadiere C. Blood 97:1925-1928(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ILE-249. |
| [16] | "The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration." Tuo J., Smith B.C., Bojanowski C.M., Meleth A.D., Gery I., Csaky K.G., Chew E.Y., Chan C.C. FASEB J. 18:1297-1299(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ILE-249 AND MET-280, ASSOCIATION WITH ARMD12. |
| [17] | "CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration." Combadiere C., Feumi C., Raoul W., Keller N., Rodero M., Pezard A., Lavalette S., Houssier M., Jonet L., Picard E., Debre P., Sirinyan M., Deterre P., Ferroukhi T., Cohen S.Y., Chauvaud D., Jeanny J.C., Chemtob S., Behar-Cohen F., Sennlaub F. J. Clin. Invest. 117:2920-2928(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ILE-249 AND MET-280, EFFECT ON CHEMOTAXIS OF MONOCYTES OF ARMD12 PATIENTS. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | 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. |
| IPI | IPI00026498. IPI00409704. IPI00930189. |
| PIR | JC4304. |
| RefSeq | NP_001164642.1. NM_001171171.1. NP_001164643.1. NM_001171172.1. NP_001164645.1. NM_001171174.1. NP_001328.1. NM_001337.3. |
| UniGene | Hs.78913. |
3D structure databases | |
| ProteinModelPortal | P49238. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-5879N. |
| STRING | 9606.ENSP00000382166. |
Protein family/group databases | |
| GPCRDB | Search... |
PTM databases | |
| PhosphoSite | P49238. |
Polymorphism databases | |
| DMDM | 1351394. |
Proteomic databases | |
| PaxDb | P49238. |
| PRIDE | P49238. |
Protocols and materials databases | |
| DNASU | 1524. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000358309; ENSP00000351059; ENSG00000168329. ENST00000399220; ENSP00000382166; ENSG00000168329. ENST00000541347; ENSP00000439140; ENSG00000168329. ENST00000542107; ENSP00000444928; ENSG00000168329. |
| GeneID | 1524. |
| KEGG | hsa:1524. |
| UCSC | uc003cjl.3. human. uc021wwc.1. human. |
Organism-specific databases | |
| CTD | 1524. |
| GeneCards | GC03M039279. |
| HGNC | HGNC:2558. CX3CR1. |
| HPA | CAB032478. |
| MIM | 601470. gene. 609423. phenotype. 613784. phenotype. |
| neXtProt | NX_P49238. |
| Orphanet | 279. Age-related macular degeneration. |
| PharmGKB | PA27054. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG151350. |
| HOGENOM | HOG000234122. |
| HOVERGEN | HBG106917. |
| InParanoid | P49238. |
| KO | K04192. |
| OMA | APQFMFT. |
| OrthoDB | EOG4WM4VB. |
Enzyme and pathway databases | |
| Reactome | REACT_111102. Signal Transduction. |
Gene expression databases | |
| ArrayExpress | P49238. |
| Bgee | P49238. |
| CleanEx | HS_CX3CR1. |
| Genevestigator | P49238. |
| GermOnline | ENSG00000168329. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005387. Chemokine_CX3CR1. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view] |
| Pfam | PF00001. 7tm_1. 1 hit. [Graphical view] |
| PRINTS | PR01562. FRACTALKINER. PR00237. GPCRRHODOPSN. |
| PROSITE | PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| BindingDB | P49238. |
| ChEMBL | CHEMBL4843. |
| GenomeRNAi | 1524. |
| NextBio | 35535042. |
| SOURCE | Search... |
Entry information
| Entry name | CX3C1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P49238 Secondary accession number(s): A0N0N6, B2R5Z4, J3KP17 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| 7-transmembrane G-linked receptors List of 7-transmembrane G-linked receptor entries |
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
