ID CCR5_HUMAN Reviewed; 352 AA. AC P51681; O14692; O14693; O14695; O14696; O14697; O14698; O14699; O14700; AC O14701; O14702; O14703; O14704; O14705; O14706; O14707; O14708; O15538; AC Q9UPA4; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 221. DE RecName: Full=C-C chemokine receptor type 5 {ECO:0000305}; DE Short=C-C CKR-5; DE Short=CC-CKR-5; DE Short=CCR-5; DE Short=CCR5; DE AltName: Full=CHEMR13; DE AltName: Full=HIV-1 fusion coreceptor; DE AltName: CD_antigen=CD195; GN Name=CCR5 {ECO:0000312|HGNC:HGNC:1606}; Synonyms=CMKBR5; 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 [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=8639485; DOI=10.1021/bi952950g; RA Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M.; RT "Molecular cloning and functional expression of a new human CC-chemokine RT receptor gene."; RL Biochemistry 35:3362-3367(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL4 AND CCL5, AND RP TISSUE SPECIFICITY. RC TISSUE=Macrophage; RX PubMed=8663314; DOI=10.1074/jbc.271.29.17161; RA Raport C.J., Gosling J., Schweichart V.L., Gray P.W., Charo I.F.; RT "Molecular cloning and functional characterization of a novel human CC RT chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha."; RL J. Biol. Chem. 271:17161-17166(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH CCL3; CCL4 AND RP CCL5. RX PubMed=8699119; DOI=10.1002/jlb.60.1.147; RA Combadiere C., Ahuja S.K., Tiffany H.L., Murphy P.M.; RT "Cloning and functional expression of CC CKR5, a human monocyte CC RT chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES."; RL J. Leukoc. Biol. 60:147-152(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9343222; DOI=10.1128/jvi.71.11.8642-8656.1997; RA Kuhmann S.E., Platt E.J., Kozak S.L., Kabat D.; RT "Polymorphisms in the CCR5 genes of African green monkeys and mice RT implicate specific amino acids in infections by simian and human RT immunodeficiency viruses."; RL J. Virol. 71:8642-8656(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND POLYMORPHISM. RX PubMed=9359654; DOI=10.1089/aid.1997.13.1357; RA Zhang L., Carruthers C.D., He T., Huang Y., Cao Y., Wang G., Hahn B., RA Ho D.D.; RT "HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism."; RL AIDS Res. Hum. Retroviruses 13:1357-1366(1997). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9388201; DOI=10.1074/jbc.272.49.30662; RA Mummidi S., Ahuja S.S., McDaniel B.L., Ahuja S.K.; RT "The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with RT 5'-end heterogeneity, dual promoter usage, and evidence for polymorphisms RT within the regulatory regions and noncoding exons."; RL J. Biol. Chem. 272:30662-30671(1997). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-178. RX PubMed=10917742; DOI=10.1016/s1286-4579(99)80002-1; RA Magierowska M., Lepage V., Lien T.X., Lan N.T., Guillotel M., Issafras H., RA Reynes J.M., Fleury H.J., Chi N.H., Follezou J.Y., Debre P., Theodorou I., RA Barre-Sinoussi F.; RT "Novel variant of the CCR5 gene in a Vietnamese population."; RL Microbes Infect. 1:123-124(1999). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [9] 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 [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 [11] RP INVOLVEMENT IN RESISTANCE OR SUSCEPTIBILITY TO HIV-1. RX PubMed=8756719; DOI=10.1016/s0092-8674(00)80110-5; RA Liu R., Paxton W.A., Choe S., Ceradini D., Martin S.R., Horuk R., RA MacDonald M.E., Stuhlmann H., Koup R.A., Landau N.R.; RT "Homozygous defect in HIV-1 coreceptor accounts for resistance of some RT multiply-exposed individuals to HIV-1 infection."; RL Cell 86:367-377(1996). RN [12] RP FUNCTION AS A HIV-1 CORECEPTOR. RX PubMed=8649511; DOI=10.1038/381661a0; RA Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., RA di Marzio P., Marmon S., Sutton R.E., Hill C.M., Davis C.B., Peiper S.C., RA Schall T.J., Littman D.R., Landau N.R.; RT "Identification of a major co-receptor for primary isolates of HIV-1."; RL Nature 381:661-666(1996). RN [13] RP FUNCTION AS A HIV-1 CORECEPTOR. RX PubMed=8649512; DOI=10.1038/381667a0; RA Dragic T., Litwin V., Allaway G.P., Martin S.R., Huang Y., Nagashima K.A., RA Cayanan C., Maddon P.J., Koup R.A., Moore J.P., Paxton W.A.; RT "HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR- RT 5."; RL Nature 381:667-673(1996). RN [14] RP INVOLVEMENT IN RESISTANCE OR SUSCEPTIBILITY TO HIV-1. RX PubMed=8751444; DOI=10.1038/382722a0; RA Samson M., Libert F., Doranz B.J., Rucker J., Liesnard C., Farber C.M., RA Saragosti S., Lapoumeroulie C., Cognaux J., Forceille C., Muyldermans G., RA Verhofstede C., Burtonboy G., Georges M., Imai T., Rana S., Yi Y., RA Smyth R.J., Collman R.G., Doms R.W., Vassart G., Parmentier M.; RT "Resistance to HIV-1 infection in caucasian individuals bearing mutant RT alleles of the CCR-5 chemokine receptor gene."; RL Nature 382:722-725(1996). RN [15] RP INTERACTION WITH HIV-1 SURFACE PROTEIN GP120, AND FUNCTION (MICROBIAL RP INFECTION). RX PubMed=9632396; DOI=10.1126/science.280.5371.1949; RA Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D., RA Hendrickson W.A., Sodroski J.; RT "A conserved HIV gp120 glycoprotein structure involved in chemokine RT receptor binding."; RL Science 280:1949-1953(1998). RN [16] RP SULFATION AT TYR-3, GLYCOSYLATION, AND MUTAGENESIS OF TYR-3; TYR-10; TYR-14 RP AND TYR-15. RX PubMed=10089882; DOI=10.1016/s0092-8674(00)80577-2; RA Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M., RA Gerard N.P., Gerard C., Sodroski J., Choe H.; RT "Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 RT entry."; RL Cell 96:667-676(1999). RN [17] RP PHOSPHORYLATION AT SER-336; SER-337; SER-342 AND SER-349, MUTAGENESIS OF RP SER-336; SER-337; SER-342 AND SER-349, AND INTERACTION WITH GRK2. RX PubMed=10085131; DOI=10.1074/jbc.274.13.8875; RA Oppermann M., Mack M., Proudfoot A.E., Olbrich H.; RT "Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) RT phosphorylation and identification of phosphorylation sites on the CCR5 RT carboxyl terminus."; RL J. Biol. Chem. 274:8875-8885(1999). RN [18] RP FUNCTION, FUNCTION (MICROBIAL INFECTION), MUTAGENESIS OF CYS-20; CYS-101; RP CYS-178 AND CYS-269, SUBCELLULAR LOCATION, AND INTERACTION WITH CCL4. RX PubMed=10383387; DOI=10.1074/jbc.274.27.18902; RA Blanpain C., Lee B., Vakili J., Doranz B.J., Govaerts C., Migeotte I., RA Sharron M., Dupriez V., Vassart G., Doms R.W., Parmentier M.; RT "Extracellular cysteines of CCR5 are required for chemokine binding, but RT dispensable for HIV-1 coreceptor activity."; RL J. Biol. Chem. 274:18902-18908(1999). RN [19] RP PALMITOYLATION AT CYS-321; CYS-323 AND CYS-324, SUBCELLULAR LOCATION, RP FUNCTION, AND MUTAGENESIS OF CYS-321; CYS-323 AND CYS-324. RX PubMed=11323418; DOI=10.1074/jbc.m100583200; RA Blanpain C., Wittamer V., Vanderwinden J.-M., Boom A., Renneboog B., RA Lee B., Le Poul E., El Asmar L., Govaerts C., Vassart G., Doms R.W., RA Parmentier M.; RT "Palmitoylation of CCR5 is critical for receptor trafficking and efficient RT activation of intracellular signaling pathways."; RL J. Biol. Chem. 276:23795-23804(2001). RN [20] RP INTERACTION WITH ARRB2, AND MUTAGENESIS OF SER-336; SER-337; SER-342 AND RP SER-349. RX PubMed=11448957; DOI=10.1074/jbc.m102782200; RA Kraft K., Olbrich H., Majoul I., Mack M., Proudfoot A., Oppermann M.; RT "Characterization of sequence determinants within the carboxyl-terminal RT domain of chemokine receptor CCR5 that regulate signaling and receptor RT internalization."; RL J. Biol. Chem. 276:34408-34418(2001). RN [21] RP SULFATION, GLYCOSYLATION AT SER-6 AND SER-7, INTERACTION WITH CCL3; CCL4 RP AND CCL5, MUTAGENESIS OF TYR-3; 6-SER-SER-7; SER-6; SER-7; TYR-10; TYR-14; RP TYR-15 AND 16-THR-SER-17, AND CHARACTERIZATION OF VARIANT ASP-10. RX PubMed=11733580; DOI=10.1084/jem.194.11.1661; RA Bannert N., Craig S., Farzan M., Sogah D., Santo N.V., Choe H., RA Sodroski J.; RT "Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of RT CC chemokine receptor 5 contribute to high affinity binding of RT chemokines."; RL J. Exp. Med. 194:1661-1673(2001). RN [22] RP INTERACTION WITH PRAF2. RX PubMed=15757671; DOI=10.1016/j.febslet.2005.02.037; RA Schweneker M., Bachmann A.S., Moelling K.; RT "JM4 is a four-transmembrane protein binding to the CCR5 receptor."; RL FEBS Lett. 579:1751-1758(2005). RN [23] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=16144840; DOI=10.1074/jbc.m500535200; RA Huettenrauch F., Pollok-Kopp B., Oppermann M.; RT "G protein-coupled receptor kinases promote phosphorylation and beta- RT arrestin-mediated internalization of CCR5 homo- and hetero-oligomers."; RL J. Biol. Chem. 280:37503-37515(2005). RN [24] RP INVOLVEMENT IN WEST NILE VIRUS INFECTION SUSCEPTIBILITY. RX PubMed=16418398; DOI=10.1084/jem.20051970; RA Glass W.G., McDermott D.H., Lim J.K., Lekhong S., Yu S.F., Frank W.A., RA Pape J., Cheshier R.C., Murphy P.M.; RT "CCR5 deficiency increases risk of symptomatic West Nile virus infection."; RL J. Exp. Med. 203:35-40(2006). RN [25] RP INDUCTION (MICROBIAL INFECTION), AND INTERACTION WITH HHV-5 PROTEIN UL78. RX PubMed=22496149; DOI=10.1182/blood-2011-08-372516; RA Tadagaki K., Tudor D., Gbahou F., Tschische P., Waldhoer M., Bomsel M., RA Jockers R., Kamal M.; RT "Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 RT and CXCR4 impairing their HIV coreceptor activity."; RL Blood 119:4908-4918(2012). RN [26] RP INTERACTION WITH CNIH4. RX PubMed=24405750; DOI=10.1111/tra.12148; RA Sauvageau E., Rochdi M.D., Oueslati M., Hamdan F.F., Percherancier Y., RA Simpson J.C., Pepperkok R., Bouvier M.; RT "CNIH4 interacts with newly synthesized GPCR and controls their export from RT the endoplasmic reticulum."; RL Traffic 15:383-400(2014). RN [27] RP FUNCTION, AND INTERACTION WITH S100A4. RX PubMed=30713770; RA Sharapova T.N., Romanova E.A., Sashchenko L.P., Yashin D.V.; RT "Tag7-Mts1 Complex Induces Lymphocytes Migration via CCR5 and CXCR3 RT Receptors."; RL Acta Naturae 10:115-120(2018). RN [28] RP 3D-STRUCTURE MODELING. RX PubMed=12496074; DOI=10.1016/s0006-3495(02)75307-1; RA Paterlini M.G.; RT "Structure modeling of the chemokine receptor CCR5: implications for ligand RT binding and selectivity."; RL Biophys. J. 83:3012-3031(2002). RN [29] RP 3D-STRUCTURE MODELING. RX PubMed=14517611; DOI=10.1007/s00894-003-0154-9; RA Liu S., Fan S., Sun Z.; RT "Structural and functional characterization of the human CCR5 receptor in RT complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular RT modeling studies."; RL J. Mol. Model. 9:329-336(2003). RN [30] RP STRUCTURE BY NMR OF 1-27 IN COMPLEX WITH HIV-1 GP120 AND CD4 MIMIC PEPTIDE, RP FUNCTION (MICROBIAL INFECTION), AND SULFATION AT TYR-10 AND TYR-14. RX PubMed=21763489; DOI=10.1016/j.jmb.2011.04.023; RA Schnur E., Noah E., Ayzenshtat I., Sargsyan H., Inui T., Ding F.X., RA Arshava B., Sagi Y., Kessler N., Levy R., Scherf T., Naider F., RA Anglister J.; RT "The conformation and orientation of a 27-residue CCR5 peptide in a ternary RT complex with HIV-1 gp120 and a CD4-mimic peptide."; RL J. Mol. Biol. 410:778-797(2011). RN [31] {ECO:0007744|PDB:4MBS} RP X-RAY CRYSTALLOGRAPHY (2.71 ANGSTROMS) OF 2-223 AND 227-352 IN COMPLEX WITH RP DRUG, AND DISULFIDE BONDS. RX PubMed=24030490; DOI=10.1126/science.1241475; RA Tan Q., Zhu Y., Li J., Chen Z., Han G.W., Kufareva I., Li T., Ma L., RA Fenalti G., Li J., Zhang W., Xie X., Yang H., Jiang H., Cherezov V., RA Liu H., Stevens R.C., Zhao Q., Wu B.; RT "Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc RT complex."; RL Science 341:1387-1390(2013). RN [32] RP VARIANTS GLN-55; LEU-215; GLN-223; VAL-335 AND PHE-339. RX PubMed=9207783; DOI=10.1038/ng0797-221; RA Ansari-Lari M.A., Liu X.-M., Metzker M.L., Rut A.R., Gibbs R.A.; RT "The extent of genetic variation in the CCR5 gene."; RL Nat. Genet. 16:221-222(1997). RN [33] RP VARIANTS LEU-12; SER-20; SER-29; PHE-42; GLN-55; SER-60; VAL-73; GLN-223; RP LYS-228 DEL; VAL-301; VAL-335 AND PHE-339, AND ASSOCIATION WITH RP SUSCEPTIBILITY TO HIV-1. RX PubMed=9399903; DOI=10.1086/301645; RA Carrington M., Kissner T., Gerrard B., Ivanov S., O'Brien S.J., Dean M.; RT "Novel alleles of the chemokine-receptor gene CCR5."; RL Am. J. Hum. Genet. 61:1261-1267(1997). RN [34] RP CHARACTERIZATION OF VARIANT SER-60. RX PubMed=11369664; DOI=10.1182/blood.v97.11.3651; RA Tamasauskas D., Powell V., Saksela K., Yazdanbakhsh K.; RT "A homologous naturally occurring mutation in Duffy and CCR5 leading to RT reduced receptor expression."; RL Blood 97:3651-3654(2001). RN [35] RP INVOLVEMENT IN RESISTANCE TO HIV-1 INFECTION, VARIANT ARG-106, AND RP CHARACTERIZATION OF VARIANTS ARG-106 AND ARG-178. RX PubMed=17092330; DOI=10.1186/1742-4690-3-81; RA Saez-Cirion A., Versmisse P., Truong L.X., Chakrabarti L.A., Carpentier W., RA Barre-Sinoussi F., Scott-Algara D., Pancino G.; RT "Persistent resistance to HIV-1 infection in CD4 T cells from exposed RT uninfected Vietnamese individuals is mediated by entry and post-entry RT blocks."; RL Retrovirology 3:81-81(2006). RN [36] RP INVOLVEMENT IN T1D22. RX PubMed=19073967; DOI=10.1056/nejmoa0807917; RA Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., Yang J.H.M., RA Howson J.M.M., Stevens H., McManus R., Wijmenga C., Heap G.A., Dubois P.C., RA Clayton D.G., Hunt K.A., van Heel D.A., Todd J.A.; RT "Shared and distinct genetic variants in type 1 diabetes and celiac RT disease."; RL N. Engl. J. Med. 359:2767-2777(2008). CC -!- FUNCTION: Receptor for a number of inflammatory CC-chemokines including CC CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently CC transduces a signal by increasing the intracellular calcium ion level. CC May play a role in the control of granulocytic lineage proliferation or CC differentiation. Participates in T-lymphocyte migration to the CC infection site by acting as a chemotactic receptor (PubMed:30713770). CC {ECO:0000269|PubMed:10383387, ECO:0000269|PubMed:11323418, CC ECO:0000269|PubMed:30713770, ECO:0000269|PubMed:8639485, CC ECO:0000269|PubMed:8663314, ECO:0000269|PubMed:8699119}. CC -!- FUNCTION: (Microbial infection) Acts as a coreceptor (CD4 being the CC primary receptor) of human immunodeficiency virus-1/HIV-1. CC {ECO:0000269|PubMed:10383387, ECO:0000269|PubMed:21763489, CC ECO:0000269|PubMed:8649511, ECO:0000269|PubMed:8649512, CC ECO:0000269|PubMed:9632396}. CC -!- SUBUNIT: Interacts with PRAF2 (PubMed:15757671). Efficient ligand CC binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O- CC glycosylation and sialic acid modifications. Glycosylation on Ser-6 is CC required for efficient binding of CCL4 (PubMed:11733580, CC PubMed:8663314, PubMed:8699119, PubMed:10383387). Interacts with GRK2 CC (PubMed:10085131). Interacts with ARRB1 and ARRB2 (PubMed:11448957, CC PubMed:16144840). Interacts with CNIH4 (PubMed:24405750). Interacts CC with S100A4; this interaction stimulates T-lymphocyte chemotaxis CC (PubMed:30713770). {ECO:0000269|PubMed:10085131, CC ECO:0000269|PubMed:10383387, ECO:0000269|PubMed:11448957, CC ECO:0000269|PubMed:11733580, ECO:0000269|PubMed:15757671, CC ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:24405750, CC ECO:0000269|PubMed:30713770, ECO:0000269|PubMed:8663314, CC ECO:0000269|PubMed:8699119}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 surface protein CC gp120. {ECO:0000269|PubMed:21763489, ECO:0000269|PubMed:9632396}. CC -!- SUBUNIT: (Microbial infection) May interact with human CC cytomegalovirus/HHV-5 protein UL78. {ECO:0000269|PubMed:22496149}. CC -!- INTERACTION: CC P51681; Q16570-2: ACKR1; NbExp=3; IntAct=EBI-489374, EBI-21403047; CC P51681; Q92583: CCL17; NbExp=2; IntAct=EBI-489374, EBI-16640146; CC P51681; PRO_0000005165 [P13236]: CCL4; NbExp=2; IntAct=EBI-489374, EBI-6625160; CC P51681; P13501: CCL5; NbExp=6; IntAct=EBI-489374, EBI-2848366; CC P51681; P51681: CCR5; NbExp=3; IntAct=EBI-489374, EBI-489374; CC P51681; P01730: CD4; NbExp=3; IntAct=EBI-489374, EBI-353826; CC P51681; P61073: CXCR4; NbExp=4; IntAct=EBI-489374, EBI-489411; CC P51681; P54849: EMP1; NbExp=3; IntAct=EBI-489374, EBI-4319440; CC P51681; O54081: lukE; Xeno; NbExp=2; IntAct=EBI-489374, EBI-16027720; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10383387, CC ECO:0000269|PubMed:11323418}; Multi-pass membrane protein CC {ECO:0000269|PubMed:11323418}. CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, thymus, in the myeloid CC cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CC CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small CC intestine. Low levels in ovary and lung. {ECO:0000269|PubMed:8639485, CC ECO:0000269|PubMed:8663314}. CC -!- INDUCTION: (Microbial infection) May be down-regulated by human CC cytomegalovirus/HHV-5 protein UL78. {ECO:0000269|PubMed:22496149}. CC -!- PTM: Sulfated on at least 2 of the N-terminal tyrosines. Sulfation CC contributes to the efficiency of HIV-1 entry and is required for CC efficient binding of the chemokines, CCL3 and CCL4. CC {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580, CC ECO:0000269|PubMed:21763489}. CC -!- PTM: O-glycosylated, but not N-glycosylated. Ser-6 appears to be the CC major site even if Ser-7 may be also O-glycosylated. Also sialylated CC glycans present which contribute to chemokine binding. Thr-16 and Ser- CC 17 may also be glycosylated and, if so, with small moieties such as a CC T-antigen. {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580}. CC -!- PTM: Palmitoylation in the C-terminal is important for cell surface CC expression, and to a lesser extent, for HIV entry. CC {ECO:0000269|PubMed:11323418}. CC -!- PTM: Phosphorylation on serine residues in the C-terminal is stimulated CC by binding CC chemokines especially by APO-RANTES. CC {ECO:0000269|PubMed:10085131}. CC -!- POLYMORPHISM: Variations in CCR5 are associated with resistance or CC susceptibility to immunodeficiency virus type 1 (resistance or CC susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene also CC influence the rate of progression to AIDS after infection. CC {ECO:0000269|PubMed:17092330, ECO:0000269|PubMed:8751444, CC ECO:0000269|PubMed:8756719}. CC -!- POLYMORPHISM: Variations in CCR5 are associated with susceptibility to CC West Nile virus (WNV) infection [MIM:610379]. CC {ECO:0000269|PubMed:16418398}. CC -!- DISEASE: Type 1 diabetes mellitus 22 (T1D22) [MIM:612522]: A CC multifactorial disorder of glucose homeostasis that is characterized by CC susceptibility to ketoacidosis in the absence of insulin therapy. CC Clinical features are polydipsia, polyphagia and polyuria which result CC from hyperglycemia-induced osmotic diuresis and secondary thirst. These CC derangements result in long-term complications that affect the eyes, CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:19073967}. 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=Wikipedia; Note=CC chemokine receptors entry; CC URL="https://en.wikipedia.org/wiki/CC_chemokine_receptors"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCR5 receptor entry; CC URL="https://en.wikipedia.org/wiki/CCR5"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X91492; CAA62796.1; -; Genomic_DNA. DR EMBL; U54994; AAC50598.1; -; mRNA. DR EMBL; U57840; AAB17071.1; -; mRNA. DR EMBL; U83326; AAC51797.1; -; Genomic_DNA. DR EMBL; AF011500; AAB65700.1; -; mRNA. DR EMBL; AF011501; AAB65701.1; -; mRNA. DR EMBL; AF011502; AAB65702.1; -; mRNA. DR EMBL; AF011503; AAB65703.1; -; mRNA. DR EMBL; AF011505; AAB65705.1; -; mRNA. DR EMBL; AF011506; AAB65706.1; -; mRNA. DR EMBL; AF011507; AAB65707.1; -; mRNA. DR EMBL; AF011508; AAB65708.1; -; mRNA. DR EMBL; AF011509; AAB65709.1; -; mRNA. DR EMBL; AF011510; AAB65710.1; -; mRNA. DR EMBL; AF011511; AAB65711.1; -; mRNA. DR EMBL; AF011512; AAB65712.1; -; mRNA. DR EMBL; AF011513; AAB65713.1; -; mRNA. DR EMBL; AF011514; AAB65714.1; -; mRNA. DR EMBL; AF011515; AAB65715.1; -; mRNA. DR EMBL; AF011516; AAB65716.1; -; mRNA. DR EMBL; AF011517; AAB65717.1; -; mRNA. DR EMBL; AF011518; AAB65718.1; -; mRNA. DR EMBL; AF011519; AAB65719.1; -; mRNA. DR EMBL; AF011520; AAB65720.1; -; mRNA. DR EMBL; AF011521; AAB65721.1; -; mRNA. DR EMBL; AF011522; AAB65722.1; -; mRNA. DR EMBL; AF011523; AAB65723.1; -; mRNA. DR EMBL; AF011524; AAB65724.1; -; mRNA. DR EMBL; AF011525; AAB65725.1; -; mRNA. DR EMBL; AF011526; AAB65726.1; -; mRNA. DR EMBL; AF011527; AAB65727.1; -; mRNA. DR EMBL; AF011528; AAB65728.1; -; mRNA. DR EMBL; AF011529; AAB65729.1; -; mRNA. DR EMBL; AF011530; AAB65730.1; -; mRNA. DR EMBL; AF011531; AAB65731.1; -; mRNA. DR EMBL; AF011532; AAB65732.1; -; mRNA. DR EMBL; AF011533; AAB65733.1; -; mRNA. DR EMBL; AF011534; AAB65734.1; -; mRNA. DR EMBL; AF011535; AAB65735.1; -; mRNA. DR EMBL; AF011536; AAB65736.1; -; mRNA. DR EMBL; AF011537; AAB65737.1; -; mRNA. DR EMBL; AF031237; AAB94735.1; -; Genomic_DNA. DR EMBL; AF052539; AAD18131.1; -; Genomic_DNA. DR EMBL; AY221093; AAO65971.1; -; Genomic_DNA. DR EMBL; U95626; AAB57793.1; -; Genomic_DNA. DR EMBL; BC038398; AAH38398.1; -; mRNA. DR CCDS; CCDS2739.1; -. DR PIR; A43113; A43113. DR RefSeq; NP_000570.1; NM_000579.3. DR RefSeq; NP_001093638.1; NM_001100168.1. DR PDB; 2L87; NMR; -; A=1-27. DR PDB; 2MZX; NMR; -; A=186-195. DR PDB; 2RLL; NMR; -; A=7-15. DR PDB; 2RRS; NMR; -; A=157-174. DR PDB; 4MBS; X-ray; 2.71 A; A/B=2-352. DR PDB; 5UIW; X-ray; 2.20 A; A=2-352. DR PDB; 5YD3; X-ray; 1.35 A; B/D/F/H=11-19. DR PDB; 5YD4; X-ray; 1.35 A; B/D/F/H=11-19. DR PDB; 5YD5; X-ray; 1.96 A; B/D=11-19. DR PDB; 5YY4; X-ray; 1.59 A; B=11-19. DR PDB; 6FGP; NMR; -; A=1-27. DR PDB; 6MEO; EM; 3.90 A; B=1-313. DR PDB; 6MET; EM; 4.50 A; B=1-313. DR PDB; 7F1Q; EM; 2.90 A; R=2-319. DR PDB; 7F1R; EM; 3.00 A; R=2-319. DR PDB; 7F1S; EM; 2.80 A; R=2-319. DR PDB; 7NJZ; X-ray; 3.20 A; C=8-13. DR PDB; 7NW3; X-ray; 3.20 A; A=8-13. DR PDB; 7O7F; EM; 3.15 A; C=1-352. DR PDB; 8AS2; X-ray; 3.20 A; B=331-352. DR PDB; 8AS3; X-ray; 3.50 A; B=331-351. DR PDBsum; 2L87; -. DR PDBsum; 2MZX; -. DR PDBsum; 2RLL; -. DR PDBsum; 2RRS; -. DR PDBsum; 4MBS; -. DR PDBsum; 5UIW; -. DR PDBsum; 5YD3; -. DR PDBsum; 5YD4; -. DR PDBsum; 5YD5; -. DR PDBsum; 5YY4; -. DR PDBsum; 6FGP; -. DR PDBsum; 6MEO; -. DR PDBsum; 6MET; -. DR PDBsum; 7F1Q; -. DR PDBsum; 7F1R; -. DR PDBsum; 7F1S; -. DR PDBsum; 7NJZ; -. DR PDBsum; 7NW3; -. DR PDBsum; 7O7F; -. DR PDBsum; 8AS2; -. DR PDBsum; 8AS3; -. DR AlphaFoldDB; P51681; -. DR BMRB; P51681; -. DR EMDB; EMD-12746; -. DR EMDB; EMD-31422; -. DR EMDB; EMD-31423; -. DR EMDB; EMD-31424; -. DR EMDB; EMD-9108; -. DR EMDB; EMD-9109; -. DR SMR; P51681; -. DR BioGRID; 107639; 21. DR DIP; DIP-5866N; -. DR IntAct; P51681; 17. DR MINT; P51681; -. DR STRING; 9606.ENSP00000292303; -. DR BindingDB; P51681; -. DR ChEMBL; CHEMBL274; -. DR DrugBank; DB05501; AMD-070. DR DrugBank; DB06497; Aplaviroc. DR DrugBank; DB05906; CCR5 mAb. DR DrugBank; DB12698; Ibalizumab. DR DrugBank; DB12960; INCB-9471. DR DrugBank; DB05941; Leronlimab. DR DrugBank; DB04835; Maraviroc. DR DrugBank; DB06652; Vicriviroc. DR DrugCentral; P51681; -. DR GuidetoPHARMACOLOGY; 62; -. DR GlyCosmos; P51681; 2 sites, No reported glycans. DR GlyGen; P51681; 2 sites. DR iPTMnet; P51681; -. DR PhosphoSitePlus; P51681; -. DR SwissPalm; P51681; -. DR BioMuta; CCR5; -. DR DMDM; 1705896; -. DR jPOST; P51681; -. DR MassIVE; P51681; -. DR PaxDb; 9606-ENSP00000292303; -. DR PeptideAtlas; P51681; -. DR ProteomicsDB; 56367; -. DR ABCD; P51681; 38 sequenced antibodies. DR Antibodypedia; 29674; 2025 antibodies from 49 providers. DR DNASU; 1234; -. DR Ensembl; ENST00000292303.5; ENSP00000292303.4; ENSG00000160791.14. DR Ensembl; ENST00000445772.1; ENSP00000404881.1; ENSG00000160791.14. DR GeneID; 1234; -. DR KEGG; hsa:1234; -. DR MANE-Select; ENST00000292303.5; ENSP00000292303.4; NM_001394783.1; NP_001381712.1. DR AGR; HGNC:1606; -. DR CTD; 1234; -. DR DisGeNET; 1234; -. DR GeneCards; CCR5; -. DR HGNC; HGNC:1606; CCR5. DR HPA; ENSG00000160791; Tissue enhanced (lymphoid). DR MalaCards; CCR5; -. DR MIM; 601373; gene. DR MIM; 609423; phenotype. DR MIM; 610379; phenotype. DR MIM; 612522; phenotype. DR neXtProt; NX_P51681; -. DR OpenTargets; ENSG00000160791; -. DR PharmGKB; PA26170; -. DR VEuPathDB; HostDB:ENSG00000160791; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01020000230359; -. DR HOGENOM; CLU_009579_8_3_1; -. DR InParanoid; P51681; -. DR OMA; HYTCSPH; -. DR OrthoDB; 4604454at2759; -. DR PhylomeDB; P51681; -. DR TreeFam; TF330966; -. DR PathwayCommons; P51681; -. DR Reactome; R-HSA-173107; Binding and entry of HIV virion. DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-6783783; Interleukin-10 signaling. DR SignaLink; P51681; -. DR SIGNOR; P51681; -. DR BioGRID-ORCS; 1234; 15 hits in 1153 CRISPR screens. DR EvolutionaryTrace; P51681; -. DR GeneWiki; CCR5; -. DR GenomeRNAi; 1234; -. DR Pharos; P51681; Tclin. DR PRO; PR:P51681; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P51681; Protein. DR Bgee; ENSG00000160791; Expressed in epithelium of nasopharynx and 137 other cell types or tissues. DR ExpressionAtlas; P51681; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0019957; F:C-C chemokine binding; IPI:UniProtKB. DR GO; GO:0016493; F:C-C chemokine receptor activity; IDA:UniProtKB. DR GO; GO:0071791; F:chemokine (C-C motif) ligand 5 binding; IPI:UniProtKB. DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc. DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc. DR GO; GO:0001618; F:virus receptor activity; TAS:ProtInc. DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB. DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB. DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:BHF-UCL. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0006955; P:immune response; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0000165; P:MAPK cascade; IEP:UniProtKB. DR GO; GO:2000110; P:negative regulation of macrophage apoptotic process; IEA:Ensembl. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0070723; P:response to cholesterol; IMP:UniProtKB. DR GO; GO:0023052; P:signaling; IEP:UniProtKB. DR CDD; cd15184; 7tmA_CCR5_CCR2; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR002240; Chemokine_CCR5. DR InterPro; IPR000355; Chemokine_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR10489:SF686; C-C CHEMOKINE RECEPTOR TYPE 5; 1. DR PANTHER; PTHR10489; CELL ADHESION MOLECULE; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00657; CCCHEMOKINER. DR PRINTS; PR01110; CHEMOKINER5. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P51681; HS. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Diabetes mellitus; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; Lipoprotein; KW Membrane; Palmitate; Phosphoprotein; Receptor; Reference proteome; KW Sulfation; Transducer; Transmembrane; Transmembrane helix. FT CHAIN 1..352 FT /note="C-C chemokine receptor type 5" FT /id="PRO_0000069257" FT TOPO_DOM 1..30 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 31..58 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 59..68 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 69..89 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 90..102 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 103..124 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 125..141 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 142..166 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 167..198 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 199..218 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 219..235 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 236..260 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 261..277 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 278..301 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 302..352 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT MOD_RES 3 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:10089882" FT MOD_RES 10 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:21763489" FT MOD_RES 14 FT /note="Sulfotyrosine" FT /evidence="ECO:0000269|PubMed:21763489" FT MOD_RES 15 FT /note="Sulfotyrosine" FT /evidence="ECO:0000255" FT MOD_RES 336 FT /note="Phosphoserine; by BARK1" FT /evidence="ECO:0000269|PubMed:10085131" FT MOD_RES 337 FT /note="Phosphoserine; by BARK1" FT /evidence="ECO:0000269|PubMed:10085131" FT MOD_RES 342 FT /note="Phosphoserine; by BARK1" FT /evidence="ECO:0000269|PubMed:10085131" FT MOD_RES 349 FT /note="Phosphoserine; by BARK1" FT /evidence="ECO:0000269|PubMed:10085131" FT LIPID 321 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:11323418" FT LIPID 323 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:11323418" FT LIPID 324 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000269|PubMed:11323418" FT CARBOHYD 6 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:11733580" FT CARBOHYD 7 FT /note="O-linked (GalNAc...) serine" FT /evidence="ECO:0000269|PubMed:11733580" FT DISULFID 20..269 FT /evidence="ECO:0007744|PDB:4MBS, ECO:0007744|PDB:5UIW" FT DISULFID 101..178 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521, FT ECO:0007744|PDB:4MBS, ECO:0007744|PDB:5UIW" FT VARIANT 10 FT /note="Y -> D (in INCCR5-71A; results in absent sulfation FT and greatly decreased binding CCL4 and CCL5 when associated FT with D-3, D-10 and D-15; restored most CCL4 binding when FT associated with D-3 and D-15)" FT /evidence="ECO:0000269|PubMed:11733580" FT /id="VAR_003481" FT VARIANT 12 FT /note="I -> L" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_024066" FT VARIANT 20 FT /note="C -> S (in dbSNP:rs145061115)" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_024067" FT VARIANT 29 FT /note="A -> S (in dbSNP:rs1800939)" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_011839" FT VARIANT 31 FT /note="R -> H (in INCCR5-72A; dbSNP:rs56340326)" FT /id="VAR_003482" FT VARIANT 34 FT /note="P -> L (in TZCCR5-179)" FT /id="VAR_003483" FT VARIANT 42 FT /note="I -> F (in dbSNP:rs1475319259)" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_024068" FT VARIANT 55 FT /note="L -> Q (in dbSNP:rs1799863)" FT /evidence="ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903" FT /id="VAR_011840" FT VARIANT 60 FT /note="R -> S (risk factor for HIV-1; reduced cell surface FT expression; confers reduced susceptibility to infection by FT microbes that depend on these molecules as their receptors; FT dbSNP:rs1800940)" FT /evidence="ECO:0000269|PubMed:11369664, FT ECO:0000269|PubMed:9399903" FT /id="VAR_011841" FT VARIANT 62 FT /note="K -> R (in UGCCR5-145B)" FT /id="VAR_003484" FT VARIANT 68 FT /note="Y -> H (in ZWCCR5-7; dbSNP:rs758090461)" FT /id="VAR_003485" FT VARIANT 73 FT /note="A -> V (in dbSNP:rs56198941)" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_024069" FT VARIANT 95 FT /note="D -> N (in MWCCR5-107; dbSNP:rs149975182)" FT /id="VAR_003486" FT VARIANT 97 FT /note="G -> E (in INCCR5-467)" FT /id="VAR_003487" FT VARIANT 106 FT /note="G -> R (protects against HIV-1 infection; CD4+ FT T-cells from R-106 carriers are less susceptible to FT infection by HIV-1 R5; results in reduced CCR5 surface FT expression; dbSNP:rs183662584)" FT /evidence="ECO:0000269|PubMed:17092330" FT /id="VAR_080410" FT VARIANT 122 FT /note="L -> P (in ZWCCR5-7)" FT /id="VAR_003488" FT VARIANT 158 FT /note="F -> S (in UGCCR5-145A)" FT /id="VAR_003489" FT VARIANT 176 FT /note="Y -> C (in KECCR5-116)" FT /id="VAR_003490" FT VARIANT 177 FT /note="T -> A (in INCCR5-45C)" FT /id="VAR_003491" FT VARIANT 178 FT /note="C -> R (protects against HIV-1 infection; CD4+ FT T-cells from R-178 carriers are less susceptible to FT infection by HIV-1 R5; results in reduced CCR5 surface FT expression; dbSNP:rs199824195)" FT /evidence="ECO:0000269|PubMed:10917742, FT ECO:0000269|PubMed:17092330" FT /id="VAR_012481" FT VARIANT 185 FT /note="S -> N (in UGCCR5-145A)" FT /id="VAR_003492" FT VARIANT 210 FT /note="M -> V (in ZWCCR5-7)" FT /id="VAR_003493" FT VARIANT 214 FT /note="Y -> C (in KECCR5-3B)" FT /id="VAR_003494" FT VARIANT 215 FT /note="S -> L (in dbSNP:rs1017863136)" FT /evidence="ECO:0000269|PubMed:9207783" FT /id="VAR_024070" FT VARIANT 223 FT /note="R -> Q (in dbSNP:rs1800452)" FT /evidence="ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903" FT /id="VAR_011842" FT VARIANT 228 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_024071" FT VARIANT 239 FT /note="T -> S (in INCCR5-71A)" FT /id="VAR_003495" FT VARIANT 246 FT /note="L -> P (in UGCCR5-145A; dbSNP:rs143181119)" FT /id="VAR_003496" FT VARIANT 288 FT /note="T -> M (in INCCR5-72A; dbSNP:rs534088482)" FT /id="VAR_003497" FT VARIANT 301 FT /note="G -> V (in dbSNP:rs1800943)" FT /evidence="ECO:0000269|PubMed:9399903" FT /id="VAR_011843" FT VARIANT 302 FT /note="E -> G (in TZCCR5-179)" FT /id="VAR_003498" FT VARIANT 303 FT /note="K -> E (in THCCR5-5)" FT /id="VAR_003499" FT VARIANT 306 FT /note="N -> S (in MWCCR5-1567)" FT /id="VAR_003500" FT VARIANT 322 FT /note="K -> R (in THCCR5-5)" FT /id="VAR_003501" FT VARIANT 333 FT /note="E -> G (in THCCR5-2)" FT /id="VAR_003502" FT VARIANT 335 FT /note="A -> V (in MWCCR5-1567, MWCCR5-1568, ZWCCR5-14 and FT ZWCCR5-112; dbSNP:rs1800944)" FT /evidence="ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903" FT /id="VAR_003503" FT VARIANT 339 FT /note="Y -> F (in TZCCR5-181A and MWCCR5-107; FT dbSNP:rs1800945)" FT /evidence="ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903" FT /id="VAR_003504" FT VARIANT 345 FT /note="E -> G (in UGCCR5-145C)" FT /id="VAR_003505" FT MUTAGEN 3 FT /note="Y->D: No sulfation and strongly decreases binding FT with CCL4 and CCL5; when associated with D-10; D-14 and FT D-15. Restores most CCL4 binding; when associated with D-10 FT and D-15." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 3 FT /note="Y->F: No sulfation and strongly decreases binding FT with CCL4 and CCL5; when associated with F-10; F-14 and FT F-15." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 6..7 FT /note="SS->AA: Loss of molecular mass of 2 kDa compared to FT wild type when treated with O-glycosidase. Dramatically FT reduces binding with CCL4. Loss of molecular mass of about FT 2 kDa as compared to wild type, dramatically reduces FT binding by CCL4; when associated with A-16-17-A." FT /evidence="ECO:0000269|PubMed:11733580" FT MUTAGEN 6 FT /note="S->A: Strongly decreases CCL4 binding. No change in FT glycosylation status." FT /evidence="ECO:0000269|PubMed:11733580" FT MUTAGEN 7 FT /note="S->A: No change in glycosylation status and binds FT CCL4 as efficiently as wild type." FT /evidence="ECO:0000269|PubMed:11733580" FT MUTAGEN 10 FT /note="Y->F: No sulfation and greatly decreases binding of FT CCL4 and CCL5; when associated with F-3; F-14 and F-15. FT Small loss of sulfation; when associated with F-14 and FT F-15." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 14 FT /note="Y->D: No sulfation and greatly decreased binding of FT CCL4 and CCL5; when associated with D-3; D-10 and D-14. No FT restoration of CCL4 binding; when associated with D-10 and FT D-15." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 14 FT /note="Y->F: No sulfation and greatly decreases binding of FT CCL4 and CCL5; when associated with F-3; F-10; and F-15. FT Small loss of sulfation; when associated with F-10 and FT F-15." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 15 FT /note="Y->D: No sulfation and greatly decreased binding of FT CCL4 and CCL5; when associated with D-3; D-10 and D-14. FT Restored most CCL4 binding; when associated with D-3 and FT D-10." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 15 FT /note="Y->F: No sulfation and greatly decreases binding of FT CCL4 and CCL5; when associated with F-3; F-10 and F-14. FT Small loss of sulfation; when associated with F-10 and FT F-14." FT /evidence="ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580" FT MUTAGEN 16..17 FT /note="TS->AA: Similar decrease in molecular mass when FT treated with O-glycosidase as for wild type. Loss of FT molecular mass of about 2 kDa as compared to wild type, FT dramatically reduces binding by CCL4; when associated with FT A-6-7-A." FT /evidence="ECO:0000269|PubMed:11733580" FT MUTAGEN 20 FT /note="C->A: Decreases to 40% surface expression. No effect FT on conformational integrity. Disrupts binding of CCL4. FT Decreases cell HIV infection." FT /evidence="ECO:0000269|PubMed:10383387" FT MUTAGEN 101 FT /note="C->A: Decreases to 40% surface expression. Disrupts FT conformational integrity. Disrupts binding of CCL4. FT Decreases HIV cell infection." FT /evidence="ECO:0000269|PubMed:10383387" FT MUTAGEN 178 FT /note="C->A: Decreases to 40% surface expression. Disrupts FT conformational integrity. Disrupts binding of CCL4. FT Decreases HIV cell infection." FT /evidence="ECO:0000269|PubMed:10383387" FT MUTAGEN 269 FT /note="C->A: Decreases to 40% surface expression. No effect FT on conformational integrity. Disrupts binding of CCL4. FT Decreases cell HIV infection." FT /evidence="ECO:0000269|PubMed:10383387" FT MUTAGEN 321 FT /note="C->A: Small reduction in palmitoylation. Cell FT surface expression reduced by 50%. Greatly reduced FT palmitoylation. Cell surface expression greatly reduced; FT when associated with A-323 or A-324. No palmitoylation. FT Cell surface expression greatly reduced. HIV entry reduced FT by 50%; when associated with A-323 and A-324." FT /evidence="ECO:0000269|PubMed:11323418" FT MUTAGEN 323 FT /note="C->A: Small reduction in palmitoylation. Cell FT surface expression reduced by 50%. Greatly reduced FT palmitoylation. Cell surface expression greatly reduced; FT when associated with A-321 or A-324. No palmitoylation. FT Cell surface expression greatly reduced. HIV entry reduced FT by 50%; when associated with A-321 and A-324." FT /evidence="ECO:0000269|PubMed:11323418" FT MUTAGEN 324 FT /note="C->A: Small reduction in palmitoylation. Cell FT surface expression reduced by 50%. Greatly reduced FT palmitoylation. Cell surface expression greatly reduced; FT when associated with A-321 or A-323. No palmitoylation. FT Cell surface expression greatly reduced. HIV entry reduced FT by 50%; when associated with A-321 and A-323." FT /evidence="ECO:0000269|PubMed:11323418" FT MUTAGEN 336 FT /note="S->A: APO-RANTES-stimulated phosphorylation reduced FT by 15%; APO-RANTES-stimulated phosphorylation reduced by FT 30-50%; when associated with A-337 or A-342 or A-349; FT APO-RANTES-stimulated phosphorylation reduced by 80%; when FT associated with A-337 and A-342 or A-349; No FT APO-RANTES-stimulated phosphorylation; when associated with FT A-337; A-342 and A349; abolishes interaction with ARRB2; FT when associated with S-337; S-342 and S-349." FT /evidence="ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957" FT MUTAGEN 337 FT /note="S->A: APO-RANTES-stimulated phosphorylation reduced FT by 18%; APO-RANTES-stimulated phosphorylation reduced by FT 30-50% on APO-RANTES stimulation; when associated with FT A-336 or A-342 or A-349; APO-RANTES-stimulated FT phosphorylation reduced by 80%; when associated with A-336 FT and A-342 or A-349; No APO-RANTES-stimulated FT phosphorylation; when associated with A-336; A-342 and FT A349; abolishes interaction with ARRB2; when associated FT with S-336; S-342 and S-349." FT /evidence="ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957" FT MUTAGEN 342 FT /note="S->A: APO-RANTES-stimulated phosphorylation reduced FT by 42%. Phosphorylation reduced by 50% on APO-RANTES FT stimulation; when associated with A-336 or A-337 or A-349; FT APO-RANTES-stimulated phosphorylation reduced by 80% when FT associated with A-336 and A-337 or A-349; No FT APO-RANTES-stimulated phosphorylation; when associated with FT A-336; A-337 and A349; abolishes interaction with ARRB2; FT when associated with S-336; S-337 and S-349." FT /evidence="ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957" FT MUTAGEN 349 FT /note="S->A: APO-RANTES-stimulated phosphorylation reduced FT by 43%; APO-RANTES-stimulated phosphorylation reduced by FT 30-50%; when associated with A-336 or A-337 or A-342; FT APO-RANTES-stimulated phosphorylation reduced by 80%; when FT associated with A-336 and A-337 or A-342; No FT APO-RANTES-stimulated phosphorylation stimulation; when FT associated with A-336; A-337 and A347; abolishes FT interaction with ARRB2; when associated with S-336; S-337 FT and S-342." FT /evidence="ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957" FT HELIX 10..13 FT /evidence="ECO:0007829|PDB:2L87" FT HELIX 14..17 FT /evidence="ECO:0007829|PDB:2L87" FT TURN 20..22 FT /evidence="ECO:0007829|PDB:2L87" FT HELIX 23..57 FT /evidence="ECO:0007829|PDB:5UIW" FT TURN 58..61 FT /evidence="ECO:0007829|PDB:7F1S" FT HELIX 64..91 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 97..131 FT /evidence="ECO:0007829|PDB:5UIW" FT TURN 133..135 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 136..139 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 142..165 FT /evidence="ECO:0007829|PDB:5UIW" FT STRAND 167..172 FT /evidence="ECO:0007829|PDB:5UIW" FT STRAND 175..180 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 187..202 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 204..221 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 227..259 FT /evidence="ECO:0007829|PDB:5UIW" FT TURN 260..265 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 269..288 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 289..291 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 292..299 FT /evidence="ECO:0007829|PDB:5UIW" FT HELIX 302..313 FT /evidence="ECO:0007829|PDB:5UIW" SQ SEQUENCE 352 AA; 40524 MW; 88ECE1F38E6D45A7 CRC64; MDYQVSSPIY DINYYTSEPC QKINVKQIAA RLLPPLYSLV FIFGFVGNML VILILINCKR LKSMTDIYLL NLAISDLFFL LTVPFWAHYA AAQWDFGNTM CQLLTGLYFI GFFSGIFFII LLTIDRYLAV VHAVFALKAR TVTFGVVTSV ITWVVAVFAS LPGIIFTRSQ KEGLHYTCSS HFPYSQYQFW KNFQTLKIVI LGLVLPLLVM VICYSGILKT LLRCRNEKKR HRAVRLIFTI MIVYFLFWAP YNIVLLLNTF QEFFGLNNCS SSNRLDQAMQ VTETLGMTHC CINPIIYAFV GEKFRNYLLV FFQKHIAKRF CKCCSIFQQE APERASSVYT RSTGEQEISV GL //