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P51681 (CCR5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-C chemokine receptor type 5

Short name=C-C CKR-5
Short name=CC-CKR-5
Short name=CCR-5
Short name=CCR5
Alternative name(s):
CHEMR13
HIV-1 fusion coreceptor
CD_antigen=CD195
Gene names
Name:CCR5
Synonyms:CMKBR5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 R5 isolates. Ref.1 Ref.2 Ref.3 Ref.11 Ref.12 Ref.16

Subunit structure

Interacts with PRAF2. Interacts with HIV-1 surface protein gp120. Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with ADRBK1. Interacts with ARRB1 and ARRB2. Interacts with human cytomegalovirus/HHV-5 protein UL78. Ref.2 Ref.3 Ref.13 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.22

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.16.

Tissue specificity

Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung. Ref.1 Ref.2

Post-translational modification

Sulfated on at least 2 of the N-terminal tyrosines. Sulfation contributes to the efficiency of HIV-1 entry and is required for efficient binding of the chemokines, CCL3 and CCL4.

O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding. Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen. Ref.14 Ref.18

Palmitoylation in the C-terminal is important for cell surface expression, and to a lesser extent, for HIV entry. Ref.16

Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.

Polymorphism

Variations in CCR5 are associated with resistance or susceptibility to immunodeficiency virus type 1 (resistance or susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene also influence the rate of progression to AIDS after infection.

Ser-60 variant, a naturally occurring mutation in a conserved residue in the first intracellular domain of CCR5, results in reduced amounts of the protein in the membrane and consequently may be associated with reduced susceptibility to infection by microbes that depend on these molecules as their receptors.

Variations in CCR5 are associated with susceptibility to West Nile virus (WNV) infection [MIM:610379].

Involvement in disease

Diabetes mellitus, insulin-dependent, 22 (IDDM22) [MIM:612522]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.29

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDiabetes mellitus
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Sulfation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from mutant phenotype PubMed 19523456. Source: UniProtKB

MAPK cascade

Inferred from expression pattern PubMed 12032188. Source: UniProtKB

calcium ion transport

Inferred from direct assay Ref.3. Source: UniProtKB

calcium-mediated signaling

Inferred from direct assay PubMed 10679098PubMed 19523456. Source: UniProtKB

cell surface receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

cell-cell signaling

Inferred from direct assay PubMed 10679098. Source: UniProtKB

cellular defense response

Traceable author statement PubMed 10201901. Source: ProtInc

cellular response to lipopolysaccharide

Inferred from expression pattern PubMed 10679098. Source: UniProtKB

chemokine-mediated signaling pathway

Inferred from direct assay PubMed 11278962. Source: GOC

chemotaxis

Traceable author statement PubMed 10741397. Source: ProtInc

dendritic cell chemotaxis

Traceable author statement PubMed 16621978. Source: BHF-UCL

entry into host cell

Traceable author statement. Source: Reactome

immune response

Traceable author statement Ref.1. Source: ProtInc

inflammatory response

Traceable author statement Ref.1. Source: ProtInc

positive regulation of cytosolic calcium ion concentration

Traceable author statement PubMed 10201901. Source: ProtInc

release of sequestered calcium ion into cytosol by sarcoplasmic reticulum

Inferred from direct assay PubMed 19523456. Source: UniProtKB

response to cholesterol

Inferred from mutant phenotype PubMed 19523456. Source: UniProtKB

signaling

Inferred from expression pattern PubMed 12032188. Source: UniProtKB

viral process

Traceable author statement. Source: Reactome

   Cellular_componentcell surface

Inferred from direct assay PubMed 10521508. Source: UniProtKB

cytoplasm

Traceable author statement PubMed 10415069. Source: ProtInc

endosome

Inferred from direct assay PubMed 10679098. Source: UniProtKB

external side of plasma membrane

Inferred from direct assay PubMed 10679098PubMed 19523456. Source: UniProtKB

integral component of plasma membrane

Traceable author statement PubMed 10393923. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionC-C chemokine binding

Inferred from physical interaction PubMed 10679098Ref.3. Source: UniProtKB

C-C chemokine receptor activity

Non-traceable author statement Ref.1. Source: UniProtKB

actin binding

Inferred from direct assay PubMed 12421915. Source: UniProtKB

chemokine (C-C motif) ligand 5 binding

Inferred from physical interaction Ref.3. Source: UniProtKB

chemokine receptor activity

Traceable author statement PubMed 10201901. Source: ProtInc

coreceptor activity

Traceable author statement PubMed 10469138. Source: ProtInc

phosphatidylinositol phospholipase C activity

Traceable author statement Ref.2. Source: ProtInc

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 352352C-C chemokine receptor type 5
PRO_0000069257

Regions

Topological domain1 – 3030Extracellular Potential
Transmembrane31 – 5828Helical; Name=1; Potential
Topological domain59 – 6810Cytoplasmic Potential
Transmembrane69 – 8921Helical; Name=2; Potential
Topological domain90 – 10213Extracellular Potential
Transmembrane103 – 12422Helical; Name=3; Potential
Topological domain125 – 14117Cytoplasmic Potential
Transmembrane142 – 16625Helical; Name=4; Potential
Topological domain167 – 19832Extracellular Potential
Transmembrane199 – 21820Helical; Name=5; Potential
Topological domain219 – 23517Cytoplasmic Potential
Transmembrane236 – 26025Helical; Name=6; Potential
Topological domain261 – 27717Extracellular Potential
Transmembrane278 – 30124Helical; Name=7; Potential
Topological domain302 – 35251Cytoplasmic Potential

Amino acid modifications

Modified residue31Sulfotyrosine Ref.14
Modified residue101Sulfotyrosine Ref.25
Modified residue141Sulfotyrosine Ref.25
Modified residue151Sulfotyrosine Potential
Modified residue3361Phosphoserine; by BARK1 Ref.15
Modified residue3371Phosphoserine; by BARK1 Ref.15
Modified residue3421Phosphoserine; by BARK1 Ref.15
Modified residue3491Phosphoserine; by BARK1 Ref.15
Lipidation3211S-palmitoyl cysteine Ref.16
Lipidation3231S-palmitoyl cysteine Ref.16
Lipidation3241S-palmitoyl cysteine Ref.16
Glycosylation61O-linked (GalNAc...) Ref.18
Glycosylation71O-linked (GalNAc...) Probable
Glycosylation161O-linked (GalNAc...) Potential
Glycosylation171O-linked (GalNAc...) Potential
Disulfide bond101 ↔ 178 By similarity

Natural variations

Natural variant101Y → D in INCCR5-71A) (No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-15. Restored most CCL4 binding; when associated with D-3 and D-15. Ref.18
VAR_003481
Natural variant121I → L. Ref.27
VAR_024066
Natural variant201C → S. Ref.27
VAR_024067
Natural variant291A → S. Ref.27
Corresponds to variant rs1800939 [ dbSNP | Ensembl ].
VAR_011839
Natural variant311R → H in INCCR5-72A.
Corresponds to variant rs56340326 [ dbSNP | Ensembl ].
VAR_003482
Natural variant341P → L in TZCCR5-179.
VAR_003483
Natural variant421I → F. Ref.27
VAR_024068
Natural variant551L → Q. Ref.26 Ref.27
Corresponds to variant rs1799863 [ dbSNP | Ensembl ].
VAR_011840
Natural variant601R → S Associated with susceptibility to HIV-1; reduced surface expression and function of CCR5 protein. Ref.27 Ref.28
Corresponds to variant rs1800940 [ dbSNP | Ensembl ].
VAR_011841
Natural variant621K → R in UGCCR5-145B.
VAR_003484
Natural variant681Y → H in ZWCCR5-7.
VAR_003485
Natural variant731A → V. Ref.27
Corresponds to variant rs56198941 [ dbSNP | Ensembl ].
VAR_024069
Natural variant951D → N in MWCCR5-107.
VAR_003486
Natural variant971G → E in INCCR5-467.
VAR_003487
Natural variant1221L → P in ZWCCR5-7.
VAR_003488
Natural variant1581F → S in UGCCR5-145A.
VAR_003489
Natural variant1761Y → C in KECCR5-116.
VAR_003490
Natural variant1771T → A in INCCR5-45C.
VAR_003491
Natural variant1781C → R Found in a HIV-resistant individiual. Ref.7
Corresponds to variant rs199824195 [ dbSNP | Ensembl ].
VAR_012481
Natural variant1851S → N in UGCCR5-145A.
VAR_003492
Natural variant2101M → V in ZWCCR5-7.
VAR_003493
Natural variant2141Y → C in KECCR5-3B.
VAR_003494
Natural variant2151S → L. Ref.26
VAR_024070
Natural variant2231R → Q. Ref.26 Ref.27
Corresponds to variant rs1800452 [ dbSNP | Ensembl ].
VAR_011842
Natural variant2281Missing. Ref.27
VAR_024071
Natural variant2391T → S in INCCR5-71A.
VAR_003495
Natural variant2461L → P in UGCCR5-145A.
VAR_003496
Natural variant2881T → M in INCCR5-72A.
VAR_003497
Natural variant3011G → V. Ref.27
Corresponds to variant rs1800943 [ dbSNP | Ensembl ].
VAR_011843
Natural variant3021E → G in TZCCR5-179.
VAR_003498
Natural variant3031K → E in THCCR5-5.
VAR_003499
Natural variant3061N → S in MWCCR5-1567.
VAR_003500
Natural variant3221K → R in THCCR5-5.
VAR_003501
Natural variant3331E → G in THCCR5-2.
VAR_003502
Natural variant3351A → V in MWCCR5-1567, MWCCR5-1568, ZWCCR5-14 and ZWCCR5-112. Ref.26 Ref.27
Corresponds to variant rs1800944 [ dbSNP | Ensembl ].
VAR_003503
Natural variant3391Y → F in TZCCR5-181A and MWCCR5-107. Ref.26 Ref.27
Corresponds to variant rs1800945 [ dbSNP | Ensembl ].
VAR_003504
Natural variant3451E → G in UGCCR5-145C.
VAR_003505

Experimental info

Mutagenesis31Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-10; D-14 and D-15. Restored most CCL4 binding; when associated with D-10 and D-15. Ref.14 Ref.18
Mutagenesis31Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-10; F-14 and F-15. Ref.14 Ref.18
Mutagenesis61S → A: No change in glycosylation status and greatly decreased CCL4 binding. Loss of molecular mass of about 2 kDa as compared to wild type. Dramatically reduced binding of CCL4; when associated with A-7; A-16; A-17. Similar molecular mass loss. Dramatically reduced binding of CCL4; when associated with A-7 only. Ref.18
Mutagenesis71S → A: No change in glycosylation status and binds CCL4 as efficiently as wild type. Loss of molecular mass of about 2 kDa as compared to wild type. Dramatically reduced binding of CCL4; when associated with A-6; A-16; A-17. Similar molecular mass loss. Dramatically reduced binding of CCL4; when associated with A-6 only. Ref.18
Mutagenesis101Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-14 and F-15. Small loss of sulfation; when associated with F-14 and F-15. Ref.14 Ref.18
Mutagenesis141Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-14. No restoration of CCL4 binding; when associated with D-10 and D-15. Ref.14 Ref.18
Mutagenesis141Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10; and F-15. Small loss of sulfation; when associated with F-10 and F-15. Ref.14 Ref.18
Mutagenesis151Y → D: No sulfation and greatly decreased binding CCL4 and CCL5; when associated with D-3; D-10 and D-14. Restored most CCL4 binding; when associated with D-3 and D-10. Ref.14 Ref.18
Mutagenesis151Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-3; F-10 and F-14. Small loss of sulfation; when associated with F-10 and F-14. Ref.14 Ref.18
Mutagenesis161T → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-17. Ref.18
Mutagenesis171S → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-16. Ref.18
Mutagenesis3211C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-323 or A-324. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-323 and A-324. Ref.16
Mutagenesis3231C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-321 or A-324. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-321 and A-324. Ref.16
Mutagenesis3241C → A: Small reduction in palmitoylation. Cell surface expression reduced by 50%. Greatly reduced palmitoylation. Cell surface expression greatly reduced; when associated with A-321 or A-323. No palmitoylation. Cell surface expression greatly reduced. HIV entry reduced by 50%; when associated with A-321 and A-323. Ref.16
Mutagenesis3361S → A: APO-RANTES-stimulated phosphorylation reduced by 15%; APO-RANTES-stimulated phosphorylation reduced by 30-50%; when associated with A-337 or A-342 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-337 and A-342 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-337; A-342 and A349; abolishes interaction with ARRB2; when associated with S-337; S-342 and S-349. Ref.15 Ref.17
Mutagenesis3371S → A: APO-RANTES-stimulated phosphorylation reduced by 18%; APO-RANTES-stimulated phosphorylation reduced by 30-50% on APO-RANTES stimulation; when associated with A-336 or A-342 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-336 and A-342 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-336; A-342 and A349; abolishes interaction with ARRB2; when associated with S-336; S-342 and S-349. Ref.15 Ref.17
Mutagenesis3421S → A: APO-RANTES-stimulated phosphorylation reduced by 42%. Phosphorylation reduced by 50% on APO-RANTES stimulation; when associated with A-336 or A-337 or A-349; APO-RANTES-stimulated phosphorylation reduced by 80% when associated with A-336 and A-337 or A-349; No APO-RANTES-stimulated phosphorylation; when associated with A-336; A-337 and A349; abolishes interaction with ARRB2; when associated with S-336; S-337 and S-349. Ref.15 Ref.17
Mutagenesis3491S → A: APO-RANTES-stimulated phosphorylation reduced by 43%; APO-RANTES-stimulated phosphorylation reduced by 30-50%; when associated with A-336 or A-337 or A-342; APO-RANTES-stimulated phosphorylation reduced by 80%; when associated with A-336 and A-337 or A-342; No APO-RANTES-stimulated phosphorylation stimulation; when associated with A-336; A-337 and A347; abolishes interaction with ARRB2; when associated with S-336; S-337 and S-342. Ref.15 Ref.17

Secondary structure

..................................... 352
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P51681 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: 88ECE1F38E6D45A7

FASTA35240,524
        10         20         30         40         50         60 
MDYQVSSPIY DINYYTSEPC QKINVKQIAA RLLPPLYSLV FIFGFVGNML VILILINCKR 

        70         80         90        100        110        120 
LKSMTDIYLL NLAISDLFFL LTVPFWAHYA AAQWDFGNTM CQLLTGLYFI GFFSGIFFII 

       130        140        150        160        170        180 
LLTIDRYLAV VHAVFALKAR TVTFGVVTSV ITWVVAVFAS LPGIIFTRSQ KEGLHYTCSS 

       190        200        210        220        230        240 
HFPYSQYQFW KNFQTLKIVI LGLVLPLLVM VICYSGILKT LLRCRNEKKR HRAVRLIFTI 

       250        260        270        280        290        300 
MIVYFLFWAP YNIVLLLNTF QEFFGLNNCS SSNRLDQAMQ VTETLGMTHC CINPIIYAFV 

       310        320        330        340        350 
GEKFRNYLLV FFQKHIAKRF CKCCSIFQQE APERASSVYT RSTGEQEISV GL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and functional expression of a new human CC-chemokine receptor gene."
Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M.
Biochemistry 35:3362-3367(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY.
[2]"Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha."
Raport C.J., Gosling J., Schweichart V.L., Gray P.W., Charo I.F.
J. Biol. Chem. 271:17161-17166(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL4 AND CCL5, TISSUE SPECIFICITY.
Tissue: Macrophage.
[3]"Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES."
Combadiere C., Ahuja S.K., Tiffany H.L., Murphy P.M.
J. Leukoc. Biol. 60:147-152(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL3; CCL4 AND CCL5.
[4]"Polymorphisms in the CCR5 genes of African green monkeys and mice implicate specific amino acids in infections by simian and human immunodeficiency viruses."
Kuhmann S.E., Platt E.J., Kozak S.L., Kabat D.
J. Virol. 71:8642-8656(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism."
Zhang L., Carruthers C.D., He T., Huang Y., Cao Y., Wang G., Hahn B., Ho D.D.
AIDS Res. Hum. Retroviruses 13:1357-1366(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], POLYMORPHISM.
[6]"The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts with 5'-end heterogeneity, dual promoter usage, and evidence for polymorphisms within the regulatory regions and noncoding exons."
Mummidi S., Ahuja S.S., McDaniel B.L., Ahuja S.K.
J. Biol. Chem. 272:30662-30671(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]Magierowska M., Barre-Sinoussi F., Issafras H., Theodorou I., Debre P.
Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-178.
[8]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[9]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]"Identification of a major co-receptor for primary isolates of HIV-1."
Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., di Marzio P., Marmon S., Sutton R.E., Hill C.M., Davis C.B., Peiper S.C., Schall T.J., Littman D.R., Landau N.R.
Nature 381:661-666(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A HIV-1 CORECEPTOR.
[12]"HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5."
Dragic T., Litwin V., Allaway G.P., Martin S.R., Huang Y., Nagashima K.A., Cayanan C., Maddon P.J., Koup R.A., Moore J.P., Paxton W.A.
Nature 381:667-673(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A HIV-1 CORECEPTOR.
[13]"A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding."
Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D., Hendrickson W.A., Sodroski J.
Science 280:1949-1953(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIV-1 SURFACE PROTEIN GP120.
[14]"Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry."
Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M., Gerard N.P., Gerard C., Sodroski J., Choe H.
Cell 96:667-676(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SULFATION AT TYR-3, GLYCOSYLATION, MUTAGENESIS OF TYR-3; TYR-10; TYR-14 AND TYR-15.
[15]"Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus."
Oppermann M., Mack M., Proudfoot A.E., Olbrich H.
J. Biol. Chem. 274:8875-8885(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-336; SER-337; SER-342 AND SER-349, MUTAGENESIS OF SER-336; SER-337; SER-342 AND SER-349, INTERACTION WITH ADRBK1.
[16]"Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways."
Blanpain C., Wittamer V., Vanderwinden J.-M., Boom A., Renneboog B., Lee B., Le Poul E., El Asmar L., Govaerts C., Vassart G., Doms R.W., Parmentier M.
J. Biol. Chem. 276:23795-23804(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PALMITOYLATION AT CYS-321; CYS-323 AND CYS-324, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF CYS-321; CYS-323 AND CYS-324.
[17]"Characterization of sequence determinants within the carboxyl-terminal domain of chemokine receptor CCR5 that regulate signaling and receptor internalization."
Kraft K., Olbrich H., Majoul I., Mack M., Proudfoot A., Oppermann M.
J. Biol. Chem. 276:34408-34418(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB2, MUTAGENESIS OF SER-336; SER-337; SER-342 AND SER-349.
[18]"Sialylated O-glycans and sulfated tyrosines in the NH2-terminal domain of CC chemokine receptor 5 contribute to high affinity binding of chemokines."
Bannert N., Craig S., Farzan M., Sogah D., Santo N.V., Choe H., Sodroski J.
J. Exp. Med. 194:1661-1673(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SULFATION, GLYCOSYLATION AT SER-6, INTERACTION WITH CCL3; CCL4 AND CCL5, MUTAGENESIS OF TYR-3; SER-6; SER-7; TYR-10; TYR-14; TYR-15; THR-16 AND SER-17, CHARACTERIZATION OF VARIANT ASP-10.
[19]"JM4 is a four-transmembrane protein binding to the CCR5 receptor."
Schweneker M., Bachmann A.S., Moelling K.
FEBS Lett. 579:1751-1758(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRAF2.
[20]"G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers."
Huettenrauch F., Pollok-Kopp B., Oppermann M.
J. Biol. Chem. 280:37503-37515(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ARRB1 AND ARRB2.
[21]"CCR5 deficiency increases risk of symptomatic West Nile virus infection."
Glass W.G., McDermott D.H., Lim J.K., Lekhong S., Yu S.F., Frank W.A., Pape J., Cheshier R.C., Murphy P.M.
J. Exp. Med. 203:35-40(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN WEST NILE VIRUS INFECTION SUSCEPTIBILITY.
[22]"Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 and CXCR4 impairing their HIV coreceptor activity."
Tadagaki K., Tudor D., Gbahou F., Tschische P., Waldhoer M., Bomsel M., Jockers R., Kamal M.
Blood 119:4908-4918(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HHV-5 PROTEIN UL78.
[23]"Structure modeling of the chemokine receptor CCR5: implications for ligand binding and selectivity."
Paterlini M.G.
Biophys. J. 83:3012-3031(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[24]"Structural and functional characterization of the human CCR5 receptor in complex with HIV gp120 envelope glycoprotein and CD4 receptor by molecular modeling studies."
Liu S., Fan S., Sun Z.
J. Mol. Model. 9:329-336(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[25]"The conformation and orientation of a 27-residue CCR5 peptide in a ternary complex with HIV-1 gp120 and a CD4-mimic peptide."
Schnur E., Noah E., Ayzenshtat I., Sargsyan H., Inui T., Ding F.X., Arshava B., Sagi Y., Kessler N., Levy R., Scherf T., Naider F., Anglister J.
J. Mol. Biol. 410:778-797(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-27 IN COMPLEX WITH HIV-1 GP120 AND CD4 MIMIC PEPTIDE, SULFATION AT TYR-10 AND TYR-14.
[26]"The extent of genetic variation in the CCR5 gene."
Ansari-Lari M.A., Liu X.-M., Metzker M.L., Rut A.R., Gibbs R.A.
Nat. Genet. 16:221-222(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLN-55; LEU-215; GLN-223; VAL-335 AND PHE-339.
[27]"Novel alleles of the chemokine-receptor gene CCR5."
Carrington M., Kissner T., Gerrard B., Ivanov S., O'Brien S.J., Dean M.
Am. J. Hum. Genet. 61:1261-1267(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-12; SER-20; SER-29; PHE-42; GLN-55; SER-60; VAL-73; GLN-223; LYS-228 DEL; VAL-301; VAL-335 AND PHE-339, ASSOCIATION WITH SUSCEPTIBILITY TO HIV-1.
[28]"A homologous naturally occurring mutation in Duffy and CCR5 leading to reduced receptor expression."
Tamasauskas D., Powell V., Saksela K., Yazdanbakhsh K.
Blood 97:3651-3654(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT SER-60.
[29]"Shared and distinct genetic variants in type 1 diabetes and celiac disease."
Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., Yang J.H.M., Howson J.M.M., Stevens H., McManus R., Wijmenga C., Heap G.A., Dubois P.C., Clayton D.G., Hunt K.A., van Heel D.A., Todd J.A.
N. Engl. J. Med. 359:2767-2777(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN IDDM22.
+Additional computationally mapped references.

Web resources

Wikipedia

CC chemokine receptors entry

Wikipedia

CCR5 receptor entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X91492 Genomic DNA. Translation: CAA62796.1.
U54994 mRNA. Translation: AAC50598.1.
U57840 mRNA. Translation: AAB17071.1.
U83326 Genomic DNA. Translation: AAC51797.1.
AF011500 mRNA. Translation: AAB65700.1.
AF011501 mRNA. Translation: AAB65701.1.
AF011502 mRNA. Translation: AAB65702.1.
AF011503 mRNA. Translation: AAB65703.1.
AF011505 mRNA. Translation: AAB65705.1.
AF011506 mRNA. Translation: AAB65706.1.
AF011507 mRNA. Translation: AAB65707.1.
AF011508 mRNA. Translation: AAB65708.1.
AF011509 mRNA. Translation: AAB65709.1.
AF011510 mRNA. Translation: AAB65710.1.
AF011511 mRNA. Translation: AAB65711.1.
AF011512 mRNA. Translation: AAB65712.1.
AF011513 mRNA. Translation: AAB65713.1.
AF011514 mRNA. Translation: AAB65714.1.
AF011515 mRNA. Translation: AAB65715.1.
AF011516 mRNA. Translation: AAB65716.1.
AF011517 mRNA. Translation: AAB65717.1.
AF011518 mRNA. Translation: AAB65718.1.
AF011519 mRNA. Translation: AAB65719.1.
AF011520 mRNA. Translation: AAB65720.1.
AF011521 mRNA. Translation: AAB65721.1.
AF011522 mRNA. Translation: AAB65722.1.
AF011523 mRNA. Translation: AAB65723.1.
AF011524 mRNA. Translation: AAB65724.1.
AF011525 mRNA. Translation: AAB65725.1.
AF011526 mRNA. Translation: AAB65726.1.
AF011527 mRNA. Translation: AAB65727.1.
AF011528 mRNA. Translation: AAB65728.1.
AF011529 mRNA. Translation: AAB65729.1.
AF011530 mRNA. Translation: AAB65730.1.
AF011531 mRNA. Translation: AAB65731.1.
AF011532 mRNA. Translation: AAB65732.1.
AF011533 mRNA. Translation: AAB65733.1.
AF011534 mRNA. Translation: AAB65734.1.
AF011535 mRNA. Translation: AAB65735.1.
AF011536 mRNA. Translation: AAB65736.1.
AF011537 mRNA. Translation: AAB65737.1.
AF031237 Genomic DNA. Translation: AAB94735.1.
AF052539 Genomic DNA. Translation: AAD18131.1.
AY221093 Genomic DNA. Translation: AAO65971.1.
U95626 Genomic DNA. Translation: AAB57793.1.
BC038398 mRNA. Translation: AAH38398.1.
PIRA43113.
RefSeqNP_000570.1. NM_000579.3.
NP_001093638.1. NM_001100168.1.
UniGeneHs.450802.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ND8model-A1-352[»]
1NE0model-A1-352[»]
1OPNmodel-A1-352[»]
1OPTmodel-A1-352[»]
1OPWmodel-A1-352[»]
2L87NMR-A1-27[»]
2RLLNMR-A7-15[»]
2RRSNMR-A157-174[»]
4MBSX-ray2.71A/B3-223[»]
ProteinModelPortalP51681.
SMRP51681. Positions 19-313.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107639. 17 interactions.
DIPDIP-5866N.
IntActP51681. 11 interactions.
MINTMINT-103024.

Chemistry

BindingDBP51681.
ChEMBLCHEMBL274.
DrugBankDB04835. Maraviroc.
GuidetoPHARMACOLOGY62.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP51681.

Polymorphism databases

DMDM1705896.

Proteomic databases

PaxDbP51681.
PRIDEP51681.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292303; ENSP00000292303; ENSG00000160791.
ENST00000343801; ENSP00000343985; ENSG00000160791.
ENST00000445772; ENSP00000404881; ENSG00000160791.
GeneID1234.
KEGGhsa:1234.
UCSCuc003cpo.4. human.

Organism-specific databases

CTD1234.
GeneCardsGC03P046386.
HGNCHGNC:1606. CCR5.
MIM601373. gene.
609423. phenotype.
610379. phenotype.
612522. phenotype.
neXtProtNX_P51681.
Orphanet319269. Susceptibility/resistance to HIV infection.
PharmGKBPA26170.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG148353.
HOVERGENHBG106917.
InParanoidP51681.
KOK04180.
OMAIIFTRSQ.
OrthoDBEOG738051.
PhylomeDBP51681.
TreeFamTF330966.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
SignaLinkP51681.

Gene expression databases

ArrayExpressP51681.
BgeeP51681.
GenevestigatorP51681.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR002240. Chemokine_CCR5.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00657. CCCHEMOKINER.
PR01110. CHEMOKINER5.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51681.
GeneWikiCCR5.
GenomeRNAi1234.
NextBio5035.
PROP51681.
SOURCESearch...

Entry information

Entry nameCCR5_HUMAN
AccessionPrimary (citable) accession number: P51681
Secondary accession number(s): O14692 expand/collapse secondary AC list , O14693, O14695, O14696, O14697, O14698, O14699, O14700, O14701, O14702, O14703, O14704, O14705, O14706, O14707, O14708, O15538, Q9UPA4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries