CCR5_HUMAN
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 03-AUG-2022, entry version 212.
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; SER-6; SER-7; TYR-10; TYR-14; TYR-15;
RP THR-16 AND 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 IDDM22.
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: Ser-60 variant, a naturally occurring mutation in a
CC conserved residue in the first intracellular domain of CCR5, results in
CC reduced amounts of the protein in the membrane and consequently may be
CC associated with reduced susceptibility to infection by microbes that
CC depend on these molecules as their receptors.
CC {ECO:0000269|PubMed:11369664}.
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: Diabetes mellitus, insulin-dependent, 22 (IDDM22)
CC [MIM:612522]: A multifactorial disorder of glucose homeostasis that is
CC characterized by susceptibility to ketoacidosis in the absence of
CC insulin therapy. Clinical features are polydipsia, polyphagia and
CC polyuria which result from hyperglycemia-induced osmotic diuresis and
CC secondary thirst. These derangements result in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:19073967}. Note=Disease susceptibility is
CC associated with variants affecting the 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 ---------------------------------------------------------------------------
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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 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 AlphaFoldDB; P51681; -.
DR BMRB; P51681; -.
DR SMR; P51681; -.
DR BioGRID; 107639; 19.
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 GlyGen; P51681; 4 sites.
DR iPTMnet; P51681; -.
DR PhosphoSitePlus; P51681; -.
DR SwissPalm; P51681; -.
DR BioMuta; CCR5; -.
DR DMDM; 1705896; -.
DR jPOST; P51681; -.
DR MassIVE; P51681; -.
DR PaxDb; P51681; -.
DR PeptideAtlas; P51681; -.
DR PRIDE; P51681; -.
DR ProteomicsDB; 56367; -.
DR ABCD; P51681; 38 sequenced antibodies.
DR Antibodypedia; 29674; 1809 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 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 Orphanet; 319269; Selection of therapeutic option in AIDS.
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; 937138at2759; -.
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 1068 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 tissues.
DR ExpressionAtlas; P51681; baseline and differential.
DR Genevisible; P51681; HS.
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:0005887; C:integral component of plasma membrane; TAS:ProtInc.
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; IEA:UniProtKB-KW.
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: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 InterPro; IPR002240; Chemokine_CCR5.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR01110; CHEMOKINER5.
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 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:0000305|PubMed:11733580"
FT CARBOHYD 7
FT /note="O-linked (GalNAc...) serine"
FT /evidence="ECO:0000305|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 (associated with susceptibility to HIV-1;
FT reduced surface expression and function of CCR5 protein;
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+ T-
FT cells from R-106 carriers are less susceptible to infection
FT by HIV-1 R5; results in reduced CCR5 surface expression;
FT 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+ T-
FT cells from R-178 carriers are less susceptible to infection
FT by HIV-1 R5; results in reduced CCR5 surface expression;
FT 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 greatly decreased binding of
FT CCL4 and CCL5; when associated with D-10; D-14 and D-15.
FT Restored most CCL4 binding; when associated with D-10 and
FT D-15."
FT /evidence="ECO:0000269|PubMed:10089882,
FT ECO:0000269|PubMed:11733580"
FT MUTAGEN 3
FT /note="Y->F: No sulfation and greatly decreases binding of
FT CCL4 and CCL5; when associated with F-10; F-14 and F-15."
FT /evidence="ECO:0000269|PubMed:10089882,
FT ECO:0000269|PubMed:11733580"
FT MUTAGEN 6
FT /note="S->A: No change in glycosylation status and greatly
FT decreased CCL4 binding. Loss of molecular mass of about 2
FT kDa as compared to wild type. Dramatically reduced binding
FT of CCL4; when associated with A-7; A-16; A-17. Similar
FT molecular mass loss. Dramatically reduced binding of CCL4;
FT when associated with A-7 only."
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. Loss of molecular mass of
FT about 2 kDa as compared to wild type. Dramatically reduced
FT binding of CCL4; when associated with A-6; A-16; A-17.
FT Similar molecular mass loss. Dramatically reduced binding
FT of CCL4; when associated with A-6 only."
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 F-
FT 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 F-
FT 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 D-
FT 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 F-
FT 14."
FT /evidence="ECO:0000269|PubMed:10089882,
FT ECO:0000269|PubMed:11733580"
FT MUTAGEN 16
FT /note="T->A: Similar decrease in molecular mass when
FT treated with O-glycosidase as for wild type; when
FT associated with A-17."
FT /evidence="ECO:0000269|PubMed:11733580"
FT MUTAGEN 17
FT /note="S->A: Similar decrease in molecular mass when
FT treated with O-glycosidase as for wild type; when
FT associated with A-16."
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; APO-
FT RANTES-stimulated phosphorylation reduced by 80%; when
FT associated with A-337 and A-342 or A-349; No APO-RANTES-
FT stimulated phosphorylation; when associated with A-337; A-
FT 342 and A349; abolishes interaction with ARRB2; when
FT 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 A-
FT 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 APO-RANTES-
FT stimulated phosphorylation; when associated with A-336; A-
FT 337 and A349; abolishes interaction with ARRB2; when
FT 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; APO-
FT RANTES-stimulated phosphorylation reduced by 80%; when
FT associated with A-336 and A-337 or A-342; No APO-RANTES-
FT stimulated phosphorylation stimulation; when associated
FT with A-336; A-337 and A347; abolishes interaction with
FT ARRB2; when associated with S-336; S-337 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
