CX3C1_HUMAN
ID CX3C1_HUMAN Reviewed; 355 AA.
AC P49238; A0N0N6; B2R5Z4; J3KP17;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=CX3C chemokine receptor 1 {ECO:0000303|PubMed:12551893};
DE Short=C-X3-C CKR-1 {ECO:0000303|PubMed:12551893};
DE Short=CX3CR1 {ECO:0000303|PubMed:12551893};
DE AltName: Full=Beta chemokine receptor-like 1 {ECO:0000303|PubMed:7646814};
DE Short=CMK-BRL-1 {ECO:0000303|PubMed:7646814};
DE Short=CMK-BRL1 {ECO:0000303|PubMed:7646814};
DE AltName: Full=Fractalkine receptor {ECO:0000303|PubMed:9390561};
DE AltName: Full=G-protein coupled receptor 13;
DE AltName: Full=V28 {ECO:0000303|PubMed:7590284};
GN Name=CX3CR1 {ECO:0000303|PubMed:12551893, ECO:0000312|HGNC:HGNC:2558};
GN Synonyms=CMKBRL1 {ECO:0000303|PubMed:7646814}, GPR13;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=7590284; DOI=10.1016/0378-1119(95)00336-5;
RA Raport C.J., Schweickart V.L., Eddy R.L. Jr., Shows T.B., Gray P.W.;
RT "The orphan G-protein-coupled receptor-encoding gene V28 is closely related
RT to genes for chemokine receptors and is expressed in lymphoid and neural
RT tissues.";
RL Gene 163:295-299(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=7646814; DOI=10.1089/dna.1995.14.673;
RA Combadiere C., Ahuja S.K., Murphy P.M.;
RT "Cloning, chromosomal localization, and RNA expression of a human beta
RT chemokine receptor-like gene.";
RL DNA Cell Biol. 14:673-680(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=12551893; DOI=10.1074/jbc.m211422200;
RA DeVries M.E., Cao H., Wang J., Xu L., Kelvin A.A., Ran L., Chau L.A.,
RA Madrenas J., Hegele R.A., Kelvin D.J.;
RT "Genomic organization and evolution of the CX3CR1/CCR8 chemokine receptor
RT locus.";
RL J. Biol. Chem. 278:11985-11994(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 8-185 (ISOFORM 4), AND VARIANTS ILE-249 AND MET-280.
RC TISSUE=Amygdala, and Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Livingston R.J., Shaffer T., McFarland I., Nguyen C.P., Stanaway I.B.,
RA Rajkumar N., Johnson E.J., da Ponte S.H., Willa H., Ahearn M.O.,
RA Bertucci C., Acklestad J., Carroll A., Swanson J., Gildersleeve H.I.,
RA Nickerson D.A.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-13; ILE-249 AND
RP MET-280.
RG NIEHS SNPs program;
RL Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9390561; DOI=10.1016/s0092-8674(00)80438-9;
RA Imai T., Hieshima K., Haskell C., Baba M., Nagira M., Nishimura M.,
RA Kakizaki M., Takagi S., Nomiyama H., Schall T.J., Yoshie O.;
RT "Identification and molecular characterization of fractalkine receptor
RT CX3CR1, which mediates both leukocyte migration and adhesion.";
RL Cell 91:521-530(1997).
RN [11]
RP FUNCTION.
RX PubMed=9782118; DOI=10.1084/jem.188.8.1413;
RA Fong A.M., Robinson L.A., Steeber D.A., Tedder T.F., Yoshie O., Imai T.,
RA Patel D.D.;
RT "Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture,
RT firm adhesion, and activation under physiologic flow.";
RL J. Exp. Med. 188:1413-1419(1998).
RN [12]
RP INTERACTION WITH HRSV PROTEIN G (MICROBIAL INFECTION).
RX PubMed=11477410; DOI=10.1038/90675;
RA Tripp R.A., Jones L.P., Haynes L.M., Zheng H., Murphy P.M., Anderson L.J.;
RT "CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein.";
RL Nat. Immunol. 2:732-738(2001).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12055230; DOI=10.4049/jimmunol.168.12.6173;
RA Nishimura M., Umehara H., Nakayama T., Yoneda O., Hieshima K., Kakizaki M.,
RA Dohmae N., Yoshie O., Imai T.;
RT "Dual functions of fractalkine/CX3C ligand 1 in trafficking of
RT perforin+/granzyme B+ cytotoxic effector lymphocytes that are defined by
RT CX3CR1 expression.";
RL J. Immunol. 168:6173-6180(2002).
RN [14]
RP FUNCTION (MICROBIAL INFECTION), ALTERNATIVE SPLICING, CHARACTERIZATION
RP (ISOFORMS 2 AND 3), AND FUNCTION (ISOFORMS 2 AND 3).
RX PubMed=14607932; DOI=10.4049/jimmunol.171.10.5305;
RA Garin A., Tarantino N., Faure S., Daoudi M., Lecureuil C., Bourdais A.,
RA Debre P., Deterre P., Combadiere C.;
RT "Two novel fully functional isoforms of CX3CR1 are potent HIV
RT coreceptors.";
RL J. Immunol. 171:5305-5312(2003).
RN [15]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HIV-1 PROTEIN GP160
RP (MICROBIAL INFECTION).
RX PubMed=9726990; DOI=10.1074/jbc.273.37.23799;
RA Combadiere C., Salzwedel K., Smith E.D., Tiffany H.L., Berger E.A.,
RA Murphy P.M.;
RT "Identification of CX3CR1. A chemotactic receptor for the human CX3C
RT chemokine fractalkine and a fusion coreceptor for HIV-1.";
RL J. Biol. Chem. 273:23799-23804(1998).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14581400; DOI=10.1161/01.cir.0000097119.57756.ef;
RA Lucas A.D., Bursill C., Guzik T.J., Sadowski J., Channon K.M.,
RA Greaves D.R.;
RT "Smooth muscle cells in human atherosclerotic plaques express the
RT fractalkine receptor CX3CR1 and undergo chemotaxis to the CX3C chemokine
RT fractalkine (CX3CL1).";
RL Circulation 108:2498-2504(2003).
RN [17]
RP FUNCTION.
RX PubMed=18971423; DOI=10.1182/blood-2008-07-170787;
RA Landsman L., Bar-On L., Zernecke A., Kim K.W., Krauthgamer R.,
RA Shagdarsuren E., Lira S.A., Weissman I.L., Weber C., Jung S.;
RT "CX3CR1 is required for monocyte homeostasis and atherogenesis by promoting
RT cell survival.";
RL Blood 113:963-972(2009).
RN [18]
RP FUNCTION.
RX PubMed=20974991; DOI=10.4049/jimmunol.0904126;
RA Nakayama T., Watanabe Y., Oiso N., Higuchi T., Shigeta A., Mizuguchi N.,
RA Katou F., Hashimoto K., Kawada A., Yoshie O.;
RT "Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1.";
RL J. Immunol. 185:6472-6479(2010).
RN [19]
RP FUNCTION, BINDING TO CX3CL1, AND IDENTIFICATION IN A COMPLEX WITH INTEGRINS
RP AND CX3CL1.
RX PubMed=23125415; DOI=10.4049/jimmunol.1200889;
RA Fujita M., Takada Y.K., Takada Y.;
RT "Integrins alphavbeta3 and alpha4beta1 act as coreceptors for fractalkine,
RT and the integrin-binding defective mutant of fractalkine is an antagonist
RT of CX3CR1.";
RL J. Immunol. 189:5809-5819(2012).
RN [20]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=28791023; DOI=10.3389/fimmu.2017.00868;
RA Regis S., Caliendo F., Dondero A., Casu B., Romano F., Loiacono F.,
RA Moretta A., Bottino C., Castriconi R.;
RT "TGF-beta1 downregulates the expression of CX3CR1 by inducing miR-27a-5p in
RT primary human NK cells.";
RL Front. Immunol. 8:868-868(2017).
RN [21]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT MET-280.
RX PubMed=29326275; DOI=10.1126/science.aao1503;
RA Leonardi I., Li X., Semon A., Li D., Doron I., Putzel G., Bar A.,
RA Prieto D., Rescigno M., McGovern D.P.B., Pla J., Iliev I.D.;
RT "CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi.";
RL Science 359:232-236(2018).
RN [22]
RP VARIANTS ALA-57; ILE-122; ILE-249 AND MET-280.
RX PubMed=10731151; DOI=10.1126/science.287.5461.2274;
RA Faure S., Meyer L., Costagliola D., Vaneensberghe C., Genin E., Autran B.,
RA Delfraissy J.-F., McDermott D.H., Murphy P.M., Debre P., Theodorou I.,
RA Combadiere C.;
RT "Rapid progression to AIDS in HIV+ individuals with a structural variant of
RT the chemokine receptor CX3CR1.";
RL Science 287:2274-2277(2000).
RN [23]
RP VARIANT ILE-249.
RX PubMed=11264153; DOI=10.1182/blood.v97.7.1925;
RA Moatti D., Faure S., Fumeron F., Amara M.E.-W., Seknadji P.,
RA McDermott D.H., Debre P., Aumont M.C., Murphy P.M., de Prost D.,
RA Combadiere C.;
RT "Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor
RT for coronary artery disease.";
RL Blood 97:1925-1928(2001).
RN [24]
RP VARIANTS ILE-249 AND MET-280, AND ASSOCIATION WITH ARMD12.
RX PubMed=15208270; DOI=10.1096/fj.04-1862fje;
RA Tuo J., Smith B.C., Bojanowski C.M., Meleth A.D., Gery I., Csaky K.G.,
RA Chew E.Y., Chan C.C.;
RT "The involvement of sequence variation and expression of CX3CR1 in the
RT pathogenesis of age-related macular degeneration.";
RL FASEB J. 18:1297-1299(2004).
RN [25]
RP CHARACTERIZATION OF VARIANTS ILE-249 AND MET-280, AND EFFECT ON CHEMOTAXIS
RP OF MONOCYTES OF ARMD12 PATIENTS.
RX PubMed=17909628; DOI=10.1172/jci31692;
RA Combadiere C., Feumi C., Raoul W., Keller N., Rodero M., Pezard A.,
RA Lavalette S., Houssier M., Jonet L., Picard E., Debre P., Sirinyan M.,
RA Deterre P., Ferroukhi T., Cohen S.Y., Chauvaud D., Jeanny J.C., Chemtob S.,
RA Behar-Cohen F., Sennlaub F.;
RT "CX3CR1-dependent subretinal microglia cell accumulation is associated with
RT cardinal features of age-related macular degeneration.";
RL J. Clin. Invest. 117:2920-2928(2007).
CC -!- FUNCTION: Receptor for the C-X3-C chemokine fractalkine (CX3CL1)
CC present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts
CC distinct functions in different tissue compartments, such as immune
CC response, inflammation, cell adhesion and chemotaxis (PubMed:9390561,
CC PubMed:9782118, PubMed:12055230, PubMed:23125415). CX3CR1-CX3CL1
CC signaling mediates cell migratory functions (By similarity).
CC Responsible for the recruitment of natural killer (NK) cells to
CC inflamed tissues (By similarity). Acts as a regulator of inflammation
CC process leading to atherogenesis by mediating macrophage and monocyte
CC recruitment to inflamed atherosclerotic plaques, promoting cell
CC survival (By similarity). Involved in airway inflammation by promoting
CC interleukin 2-producing T helper (Th2) cell survival in inflamed lung
CC (By similarity). Involved in the migration of circulating monocytes to
CC non-inflamed tissues, where they differentiate into macrophages and
CC dendritic cells (By similarity). Acts as a negative regulator of
CC angiogenesis, probably by promoting macrophage chemotaxis
CC (PubMed:14581400, PubMed:18971423). Plays a key role in brain microglia
CC by regulating inflammatory response in the central nervous system (CNS)
CC and regulating synapse maturation (By similarity). Required to restrain
CC the microglial inflammatory response in the CNS and the resulting
CC parenchymal damage in response to pathological stimuli (By similarity).
CC Involved in brain development by participating in synaptic pruning, a
CC natural process during which brain microglia eliminates extra synapses
CC during postnatal development (By similarity). Synaptic pruning by
CC microglia is required to promote the maturation of circuit connectivity
CC during brain development (By similarity). Acts as an important
CC regulator of the gut microbiota by controlling immunity to intestinal
CC bacteria and fungi (By similarity). Expressed in lamina propria
CC dendritic cells in the small intestine, which form transepithelial
CC dendrites capable of taking up bacteria in order to provide defense
CC against pathogenic bacteria (By similarity). Required to initiate
CC innate and adaptive immune responses against dissemination of commensal
CC fungi (mycobiota) component of the gut: expressed in mononuclear
CC phagocytes (MNPs) and acts by promoting induction of antifungal IgG
CC antibodies response to confer protection against disseminated
CC C.albicans or C.auris infection (PubMed:29326275). Also acts as a
CC receptor for C-C motif chemokine CCL26, inducing cell chemotaxis
CC (PubMed:20974991). {ECO:0000250|UniProtKB:Q9Z0D9,
CC ECO:0000269|PubMed:12055230, ECO:0000269|PubMed:14581400,
CC ECO:0000269|PubMed:18971423, ECO:0000269|PubMed:20974991,
CC ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:29326275,
CC ECO:0000269|PubMed:9390561, ECO:0000269|PubMed:9782118}.
CC -!- FUNCTION: [Isoform 1]: (Microbial infection) Acts as coreceptor with
CC CD4 for HIV-1 virus envelope protein. {ECO:0000269|PubMed:14607932,
CC ECO:0000269|PubMed:9726990}.
CC -!- FUNCTION: [Isoform 2]: (Microbial infection) Acts as coreceptor with
CC CD4 for HIV-1 virus envelope protein (PubMed:14607932). May have more
CC potent HIV-1 coreceptothr activity than isoform 1 (PubMed:14607932).
CC {ECO:0000269|PubMed:14607932}.
CC -!- FUNCTION: [Isoform 3]: (Microbial infection) Acts as coreceptor with
CC CD4 for HIV-1 virus envelope protein (PubMed:14607932). May have more
CC potent HIV-1 coreceptor activity than isoform 1 (PubMed:14607932).
CC {ECO:0000269|PubMed:14607932}.
CC -!- SUBUNIT: Found in a ternary complex with CX3CL1 and ITGAV:ITGB3 or
CC ITGA4:ITGB1. {ECO:0000269|PubMed:23125415}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human respiratory
CC syncytial virus (HRSV) protein G; this interaction modulates host
CC immune response. {ECO:0000269|PubMed:11477410}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 envelope
CC polyprotein gp160. {ECO:0000269|PubMed:9726990}.
CC -!- INTERACTION:
CC P49238-4; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-13049264, EBI-9083477;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12055230,
CC ECO:0000269|PubMed:28791023, ECO:0000269|PubMed:9390561}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=P49238-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49238-2; Sequence=VSP_009681;
CC Name=3;
CC IsoId=P49238-3; Sequence=VSP_009682;
CC Name=4;
CC IsoId=P49238-4; Sequence=VSP_044595;
CC -!- TISSUE SPECIFICITY: Expressed in lymphoid and neural tissues
CC (PubMed:7590284). Expressed in lymphocyte subsets, such as natural
CC killer (NK) cells, gamma-delta T-cells and terminally differentiated
CC CD8(+) T-cells (PubMed:12055230). Expressed in smooth muscle cells in
CC atherosclerotic plaques (PubMed:14581400).
CC {ECO:0000269|PubMed:12055230, ECO:0000269|PubMed:14581400,
CC ECO:0000269|PubMed:7590284}.
CC -!- INDUCTION: Expression is down-regulated by miR-27a-5p microRNA in
CC natural killer (NK) cell lymphocytes in response to TGF-beta1.
CC {ECO:0000269|PubMed:28791023}.
CC -!- PTM: This protein is not N-glycosylated which is unusual for G-protein-
CC coupled receptors. {ECO:0000250|UniProtKB:P35411}.
CC -!- POLYMORPHISM: Variations in CX3CR1 are associated with rapid
CC progression to AIDS [MIM:609423]. Increased susceptibility to HIV
CC infection and rapid progression to AIDS are associated with the Ile-
CC 249/Met-280 haplotype. {ECO:0000269|PubMed:10731151}.
CC -!- DISEASE: Macular degeneration, age-related, 12 (ARMD12) [MIM:613784]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:15208270}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cx3cr1/";
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DR EMBL; U20350; AAA91783.1; -; mRNA.
DR EMBL; U28934; AAA87032.1; -; mRNA.
DR EMBL; AY016370; AAK08627.1; -; Genomic_DNA.
DR EMBL; AK312373; BAG35291.1; -; mRNA.
DR EMBL; DA413545; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; EF064744; ABK41927.1; -; Genomic_DNA.
DR EMBL; EU006531; ABS29268.1; -; Genomic_DNA.
DR EMBL; AC092053; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471055; EAW64576.1; -; Genomic_DNA.
DR EMBL; BC028078; AAH28078.1; -; mRNA.
DR CCDS; CCDS43069.1; -. [P49238-1]
DR CCDS; CCDS54571.1; -. [P49238-4]
DR PIR; JC4304; JC4304.
DR RefSeq; NP_001164642.1; NM_001171171.1. [P49238-1]
DR RefSeq; NP_001164643.1; NM_001171172.1. [P49238-1]
DR RefSeq; NP_001164645.1; NM_001171174.1. [P49238-4]
DR RefSeq; NP_001328.1; NM_001337.3. [P49238-1]
DR AlphaFoldDB; P49238; -.
DR SMR; P49238; -.
DR BioGRID; 107904; 3.
DR DIP; DIP-5879N; -.
DR IntAct; P49238; 4.
DR STRING; 9606.ENSP00000351059; -.
DR BindingDB; P49238; -.
DR ChEMBL; CHEMBL4843; -.
DR GuidetoPHARMACOLOGY; 74; -.
DR iPTMnet; P49238; -.
DR PhosphoSitePlus; P49238; -.
DR BioMuta; CX3CR1; -.
DR DMDM; 1351394; -.
DR jPOST; P49238; -.
DR MassIVE; P49238; -.
DR PaxDb; P49238; -.
DR PeptideAtlas; P49238; -.
DR PRIDE; P49238; -.
DR ProteomicsDB; 55973; -. [P49238-1]
DR ProteomicsDB; 55974; -. [P49238-2]
DR ProteomicsDB; 55975; -. [P49238-3]
DR Antibodypedia; 6554; 779 antibodies from 46 providers.
DR DNASU; 1524; -.
DR Ensembl; ENST00000358309.3; ENSP00000351059.3; ENSG00000168329.14. [P49238-4]
DR Ensembl; ENST00000399220.3; ENSP00000382166.3; ENSG00000168329.14. [P49238-1]
DR Ensembl; ENST00000541347.5; ENSP00000439140.1; ENSG00000168329.14. [P49238-1]
DR Ensembl; ENST00000542107.5; ENSP00000444928.1; ENSG00000168329.14. [P49238-1]
DR GeneID; 1524; -.
DR KEGG; hsa:1524; -.
DR MANE-Select; ENST00000399220.3; ENSP00000382166.3; NM_001337.4; NP_001328.1.
DR UCSC; uc003cjl.4; human. [P49238-1]
DR CTD; 1524; -.
DR DisGeNET; 1524; -.
DR GeneCards; CX3CR1; -.
DR HGNC; HGNC:2558; CX3CR1.
DR HPA; ENSG00000168329; Tissue enhanced (brain).
DR MalaCards; CX3CR1; -.
DR MIM; 601470; gene.
DR MIM; 609423; phenotype.
DR MIM; 613784; phenotype.
DR neXtProt; NX_P49238; -.
DR OpenTargets; ENSG00000168329; -.
DR Orphanet; 279; NON RARE IN EUROPE: Age-related macular degeneration.
DR PharmGKB; PA27054; -.
DR VEuPathDB; HostDB:ENSG00000168329; -.
DR eggNOG; ENOG502QVQK; Eukaryota.
DR GeneTree; ENSGT01020000230359; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; P49238; -.
DR OMA; FRKYLYH; -.
DR OrthoDB; 900867at2759; -.
DR PhylomeDB; P49238; -.
DR TreeFam; TF330966; -.
DR PathwayCommons; P49238; -.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR SignaLink; P49238; -.
DR SIGNOR; P49238; -.
DR BioGRID-ORCS; 1524; 13 hits in 1060 CRISPR screens.
DR ChiTaRS; CX3CR1; human.
DR GeneWiki; CX3CR1; -.
DR GenomeRNAi; 1524; -.
DR Pharos; P49238; Tchem.
DR PRO; PR:P49238; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P49238; protein.
DR Bgee; ENSG00000168329; Expressed in granulocyte and 174 other tissues.
DR ExpressionAtlas; P49238; baseline and differential.
DR Genevisible; P49238; HS.
DR GO; GO:0009986; C:cell surface; IDA:ARUK-UCL.
DR GO; GO:0097447; C:dendritic tree; ISS:ARUK-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:ARUK-UCL.
DR GO; GO:0032809; C:neuronal cell body membrane; ISS:ARUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; IBA:GO_Central.
DR GO; GO:0019960; F:C-X3-C chemokine binding; IDA:UniProtKB.
DR GO; GO:0016495; F:C-X3-C chemokine receptor activity; IDA:UniProtKB.
DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc.
DR GO; GO:0031737; F:CX3C chemokine receptor binding; IDA:UniProtKB.
DR GO; GO:0008528; F:G protein-coupled peptide receptor activity; TAS:ARUK-UCL.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:ARUK-UCL.
DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB.
DR GO; GO:0061760; P:antifungal innate immune response; IMP:UniProtKB.
DR GO; GO:0035425; P:autocrine signaling; ISS:ARUK-UCL.
DR GO; GO:0007420; P:brain development; ISS:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; IDA:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ARUK-UCL.
DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:ARUK-UCL.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl.
DR GO; GO:0021626; P:central nervous system maturation; ISS:ARUK-UCL.
DR GO; GO:0006935; P:chemotaxis; IGI:ARUK-UCL.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0048874; P:host-mediated regulation of intestinal microbiota composition; ISS:UniProtKB.
DR GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IC:ARUK-UCL.
DR GO; GO:0030595; P:leukocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:0050901; P:leukocyte tethering or rolling; ISS:ARUK-UCL.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; ISS:UniProtKB.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; ISS:ARUK-UCL.
DR GO; GO:0150090; P:multiple spine synapse organization, single dendrite; ISS:ARUK-UCL.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl.
DR GO; GO:0110091; P:negative regulation of hippocampal neuron apoptotic process; ISS:ARUK-UCL.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; ISS:ARUK-UCL.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:1904150; P:negative regulation of microglial cell mediated cytotoxicity; ISS:UniProtKB.
DR GO; GO:0007200; P:phospholipase C-activating G protein-coupled receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR GO; GO:1903721; P:positive regulation of I-kappaB phosphorylation; ISS:ARUK-UCL.
DR GO; GO:1904141; P:positive regulation of microglial cell migration; IEA:Ensembl.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISS:ARUK-UCL.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISS:ARUK-UCL.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:ARUK-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:ARUK-UCL.
DR GO; GO:1904139; P:regulation of microglial cell migration; TAS:ARUK-UCL.
DR GO; GO:0050767; P:regulation of neurogenesis; TAS:ARUK-UCL.
DR GO; GO:0045428; P:regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR GO; GO:0048167; P:regulation of synaptic plasticity; TAS:ARUK-UCL.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISS:ARUK-UCL.
DR GO; GO:0002931; P:response to ischemia; ISS:ARUK-UCL.
DR GO; GO:0009611; P:response to wounding; TAS:ProtInc.
DR GO; GO:0035176; P:social behavior; ISS:ARUK-UCL.
DR GO; GO:0060074; P:synapse maturation; ISS:ARUK-UCL.
DR GO; GO:0098883; P:synapse pruning; ISS:UniProtKB.
DR InterPro; IPR005387; Chemokine_CX3CR1.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR01562; FRACTALKINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Age-related macular degeneration; Alternative splicing;
KW Cell membrane; Disulfide bond; G-protein coupled receptor;
KW Host-virus interaction; Immunity; Inflammatory response; Innate immunity;
KW Membrane; Phosphoprotein; Receptor; Reference proteome; Transducer;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..355
FT /note="CX3C chemokine receptor 1"
FT /id="PRO_0000069326"
FT TOPO_DOM 1..31
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..59
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..69
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 70..90
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 91..103
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..125
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 126..142
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..167
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 168..195
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 196..215
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 216..231
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 232..256
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 257..273
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..297
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 298..355
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT MOD_RES 346
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0D9"
FT DISULFID 102..175
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT VAR_SEQ 1
FT /note="M -> MREPLEALKLADLDFRKSSLASGWRMASGAFTM (in isoform
FT 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_009681"
FT VAR_SEQ 1
FT /note="M -> MASGAFTM (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_009682"
FT VAR_SEQ 1
FT /note="M -> MREPLEAFKLADLDFRKSSLASGWRMASGAFTM (in isoform
FT 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044595"
FT VARIANT 13
FT /note="E -> D (in dbSNP:rs41535248)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_049386"
FT VARIANT 57
FT /note="T -> A (in dbSNP:rs199811198)"
FT /evidence="ECO:0000269|PubMed:10731151"
FT /id="VAR_010041"
FT VARIANT 122
FT /note="V -> I (in dbSNP:rs143001773)"
FT /evidence="ECO:0000269|PubMed:10731151"
FT /id="VAR_010042"
FT VARIANT 147
FT /note="V -> I (in dbSNP:rs3732380)"
FT /id="VAR_022062"
FT VARIANT 249
FT /note="V -> I (associated with a markedly reduced risk of
FT acute coronary artery disease; associated with higher risk
FT of developing ARMD12; chemotaxis of monocytes of
FT individuals with homozygous Ile-249 and Met-280 genotypes
FT is impaired in the presence of bound CX3CR1 protein;
FT dbSNP:rs3732379)"
FT /evidence="ECO:0000269|PubMed:10731151,
FT ECO:0000269|PubMed:11264153, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15208270, ECO:0000269|PubMed:17909628,
FT ECO:0000269|Ref.6"
FT /id="VAR_010043"
FT VARIANT 280
FT /note="T -> M (associated with higher risk of developing
FT ARMD12; impaired antifungal innate immune response;
FT chemotaxis of monocytes of individuals with homozygous Met-
FT 280 and Ile-249 genotypes is impaired in the presence of
FT bound CX3CR1 protein; dbSNP:rs3732378)"
FT /evidence="ECO:0000269|PubMed:10731151,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15208270,
FT ECO:0000269|PubMed:17909628, ECO:0000269|PubMed:29326275,
FT ECO:0000269|Ref.6"
FT /id="VAR_010044"
FT CONFLICT P49238-4:8
FT /note="F -> L (in Ref. 4; DA413545)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 355 AA; 40396 MW; C59DC5F4C4312F22 CRC64;
MDQFPESVTE NFEYDDLAEA CYIGDIVVFG TVFLSIFYSV IFAIGLVGNL LVVFALTNSK
KPKSVTDIYL LNLALSDLLF VATLPFWTHY LINEKGLHNA MCKFTTAFFF IGFFGSIFFI
TVISIDRYLA IVLAANSMNN RTVQHGVTIS LGVWAAAILV AAPQFMFTKQ KENECLGDYP
EVLQEIWPVL RNVETNFLGF LLPLLIMSYC YFRIIQTLFS CKNHKKAKAI KLILLVVIVF
FLFWTPYNVM IFLETLKLYD FFPSCDMRKD LRLALSVTET VAFSHCCLNP LIYAFAGEKF
RRYLYHLYGK CLAVLCGRSV HVDFSSSESQ RSRHGSVLSS NFTYHTSDGD ALLLL
