Reviewed, UniProtKB/Swiss-Prot P49238 (CX3C1_HUMAN)

Names and origin

Protein names

Recommended name:
    CX3C chemokine receptor 1
      Short name=C-X3-C CKR-1
      Short name=CX3CR1
Alternative name(s):
    Fractalkine receptor
    G-protein coupled receptor 13
    V28
    Beta chemokine receptor-like 1
    CMK-BRL-1
    CMKBLR1

Gene names

Name:	CX3CR1
Synonyms:	CMKBRL1, GPR13

Organism

Homo sapiens (Human)

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.
Sequence processing	The displayed sequence is not processed.
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.
Subcellular location	Cell membrane; Multi-pass membrane protein.
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.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc cell adhesion Traceable author statement. Source: ProtInc cellular defense response Traceable author statement. Source: ProtInc chemotaxis Traceable author statement. Source: ProtInc response to wounding Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.11 Traceable author statement. Source: ProtInc
Molecular function	chemokine receptor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 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

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	1 Potential
	Topological domain	60 – 69	10	Cytoplasmic Potential
	Transmembrane	70 – 90	21	2 Potential
	Topological domain	91 – 103	13	Extracellular Potential
	Transmembrane	104 – 125	22	3 Potential
	Topological domain	126 – 142	17	Cytoplasmic Potential
	Transmembrane	143 – 167	25	4 Potential
	Topological domain	168 – 195	28	Extracellular Potential
	Transmembrane	196 – 215	20	5 Potential
	Topological domain	216 – 231	16	Cytoplasmic Potential
	Transmembrane	232 – 256	25	6 Potential
	Topological domain	257 – 273	17	Extracellular Potential
	Transmembrane	274 – 297	24	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
	Natural variant	13	1	E → D: dbSNP rs41535248.		VAR_049386
	Natural variant	57	1	T → A Ref.13		VAR_010041
	Natural variant	122	1	V → I Ref.13		VAR_010042
	Natural variant	147	1	V → I: dbSNP rs3732380.		VAR_022062
	Natural variant	249	1	V → I Common polymorphism in Caucasian population; associated with a markedly reduced risk of acute coronary artery disease. dbSNP rs3732379.		VAR_010043
	Natural variant	280	1	T → M Common polymorphism in Caucasian population. dbSNP rs3732378.		VAR_010044

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: C59DC5F4C4312F22	FASTA	355	40,396
	10 20 30 40 50 60 MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK 70 80 90 100 110 120 KPKSVTDIYL LNLALSDLLF VATLPFWTHY LINEKGLHNA MCKFTTAFFF IGFFGSIFFI 130 140 150 160 170 180 TVISIDRYLA IVLAANSMNN RTVQHGVTIS LGVWAAAILV AAPQFMFTKQ KENECLGDYP 190 200 210 220 230 240 EVLQEIWPVL RNVETNFLGF LLPLLIMSYC YFRIIQTLFS CKNHKKAKAI KLILLVVIVF 250 260 270 280 290 300 FLFWTPYNVM IFLETLKLYD FFPSCDMRKD LRLALSVTET VAFSHCCLNP LIYAFAGEKF 310 320 330 340 350 RRYLYHLYGK CLAVLCGRSV HVDFSSSESQ RSRHGSVLSS NFTYHTSDGD ALLLL
	Isoform 2. Checksum: 446834BF5BF0FC5B	FASTA	387	43,935
	10 20 30 40 50 60 MREPLEALKL ADLDFRKSSL ASGWRMASGA FTMDQFPESV TENFEYDDLA EACYIGDIVV 70 80 90 100 110 120 FGTVFLSIFY SVIFAIGLVG NLLVVFALTN SKKPKSVTDI YLLNLALSDL LFVATLPFWT 130 140 150 160 170 180 HYLINEKGLH NAMCKFTTAF FFIGFFGSIF FITVISIDRY LAIVLAANSM NNRTVQHGVT 190 200 210 220 230 240 ISLGVWAAAI LVAAPQFMFT KQKENECLGD YPEVLQEIWP VLRNVETNFL GFLLPLLIMS 250 260 270 280 290 300 YCYFRIIQTL FSCKNHKKAK AIKLILLVVI VFFLFWTPYN VMIFLETLKL YDFFPSCDMR 310 320 330 340 350 360 KDLRLALSVT ETVAFSHCCL NPLIYAFAGE KFRRYLYHLY GKCLAVLCGR SVHVDFSSSE 370 380 SQRSRHGSVL SSNFTYHTSD GDALLLL
	Isoform 3. Checksum: 193A12DC884FC41B	FASTA	362	41,062
	10 20 30 40 50 60 MASGAFTMDQ FPESVTENFE YDDLAEACYI GDIVVFGTVF LSIFYSVIFA IGLVGNLLVV 70 80 90 100 110 120 FALTNSKKPK SVTDIYLLNL ALSDLLFVAT LPFWTHYLIN EKGLHNAMCK FTTAFFFIGF 130 140 150 160 170 180 FGSIFFITVI SIDRYLAIVL AANSMNNRTV QHGVTISLGV WAAAILVAAP QFMFTKQKEN 190 200 210 220 230 240 ECLGDYPEVL QEIWPVLRNV ETNFLGFLLP LLIMSYCYFR IIQTLFSCKN HKKAKAIKLI 250 260 270 280 290 300 LLVVIVFFLF WTPYNVMIFL ETLKLYDFFP SCDMRKDLRL ALSVTETVAF SHCCLNPLIY 310 320 330 340 350 360 AFAGEKFRRY LYHLYGKCLA VLCGRSVHVD FSSSESQRSR HGSVLSSNFT YHTSDGDALL LL

References

	« Hide 'large scale' referencesShow '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: 7590284] [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: 7646814] [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: 12551893] [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. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS ILE-249 AND MET-280. Tissue: Amygdala.
[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 for genomic applications Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASP-13; ILE-249 AND MET-280.
[7]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Blood.
[9]	"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: 11477410] [Abstract] Cited for: INTERACTION WITH HRSV PROTEIN G.
[10]	"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: 14607932] [Abstract] Cited for: ALTERNATIVE SPLICING, CHARACTERIZATION OF ISOFORMS 2 AND 3.
[11]	"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: 9390561] [Abstract] Cited for: CHARACTERIZATION.
[12]	"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: 9726990] [Abstract] Cited for: CHARACTERIZATION.
[13]	"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: 10731151] [Abstract] Cited for: VARIANTS ALA-57; ILE-122; ILE-249 AND MET-280.
[14]	"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: 11264153] [Abstract] Cited for: VARIANT ILE-249.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	U20350 mRNA. Translation: AAA91783.1. U28934 mRNA. Translation: AAA87032.1. AY016370 Genomic DNA. Translation: AAK08627.1. AK312373 mRNA. Translation: BAG35291.1. EF064744 Genomic DNA. Translation: ABK41927.1. EU006531 Genomic DNA. Translation: ABS29268.1. CH471055 Genomic DNA. Translation: EAW64576.1. BC028078 mRNA. Translation: AAH28078.1.
IPI	IPI00026498. IPI00409704. IPI00409705.
PIR	JC4304.
RefSeq	NP_001328.1.
UniGene	Hs.78913
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:5879N.
Protein family/group databases
GPCRDB	Search...
Proteomic databases
PRIDE	P49238.
Genome annotation databases
Ensembl	ENSG00000168329. Homo sapiens. [Contig view]
GeneID	1524.
KEGG	hsa:1524.
Organism-specific databases
GeneCards	GC03M039279.
H-InvDB	HIX0003188.
HGNC	HGNC:2558. CX3CR1.
MIM	601470. gene. 609423. phenotype.
PharmGKB	PA27054.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P49238.
HOVERGEN	P49238.
Enzyme and pathway databases
Reactome	REACT_14797. Signaling by GPCR.
Gene expression databases
ArrayExpress	P49238.
Bgee	P49238.
CleanEx	HS_CX3CR1.
GermOnline	ENSG00000168329. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR005387. CX3C_fract_rcpt. IPR017452. GPCR_Rhodpsn_supfam. [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 Resources
NextBio	6311.
SOURCE	Search...

Entry information

Entry name

CX3C1_HUMAN

Accession

Primary (citable) accession number: P49238
Secondary accession number(s): A0N0N6, B2R5Z4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	June 16, 2009
This is version 83 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)