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Reviewed, UniProtKB/Swiss-Prot P51681 (CCR5_HUMAN)

Last modified September 2, 2008. Version 86. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (9) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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):
    HIV-1 fusion coreceptor
    CHEMR13
    CD_antigen=CD195
Gene names
Name: CCR5
Synonyms: CMKBR5
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length352 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
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.

Subunit structure

Interacts with PRAF2. Interacts with HIV-1 surface protein gp120. Efficient ligand binding to CCL3/MIP-1alpha and CCR4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with ADRBK1.

Subcellular location

Cell membrane; Multi-pass membrane protein.

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.

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.

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

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].

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MYH9P355791EBI-489374,EBI-350338

Sequence annotation (Features)

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Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 352352C-C chemokine receptor type 5

Regions

Topological domain1 – 3030Extracellular Potential
Transmembrane31 – 58281 Potential
Topological domain59 – 6810Cytoplasmic Potential
Transmembrane69 – 89212 Potential
Topological domain90 – 10213Extracellular Potential
Transmembrane103 – 124223 Potential
Topological domain125 – 14117Cytoplasmic Potential
Transmembrane142 – 166254 Potential
Topological domain167 – 19832Extracellular Potential
Transmembrane199 – 218205 Potential
Topological domain219 – 23517Cytoplasmic Potential
Transmembrane236 – 260256 Potential
Topological domain261 – 27717Extracellular Potential
Transmembrane278 – 301247 Potential
Topological domain302 – 35251Cytoplasmic Potential

Amino acid modifications

Modified residue31Sulfotyrosine
Modified residue101Sulfotyrosine Potential
Modified residue141Sulfotyrosine Potential
Modified residue151Sulfotyrosine Potential
Modified residue3361Phosphoserine; by BARK1
Modified residue3371Phosphoserine; by BARK1
Modified residue3421Phosphoserine; by BARK1
Modified residue3491Phosphoserine; by BARK1
Lipidation3211S-palmitoyl cysteine
Lipidation3231S-palmitoyl cysteine
Lipidation3241S-palmitoyl cysteine
Glycosylation61O-linked (GalNAc...)
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.
Natural variant121I → L
Natural variant201C → S
Natural variant291A → S: dbSNP rs1800939.
Natural variant311R → H in INCCR5-72A.
Natural variant341P → L in TZCCR5-179.
Natural variant421I → F
Natural variant551L → Q: dbSNP rs1799863.
Natural variant601R → S Associated with susceptibility to HIV-1; reduced surface expression and function of CCR5 protein. dbSNP rs1800940.
Natural variant621K → R in UGCCR5-145B.
Natural variant681Y → H in ZWCCR5-7.
Natural variant731A → V
Natural variant951D → N in MWCCR5-107.
Natural variant971G → E in INCCR5-467.
Natural variant1221L → P in ZWCCR5-7.
Natural variant1581F → S in UGCCR5-145A.
Natural variant1761Y → C in KECCR5-116.
Natural variant1771T → A in INCCR5-45C.
Natural variant1781C → R Found in a HIV-resistant individiual.
Natural variant1851S → N in UGCCR5-145A.
Natural variant2101M → V in ZWCCR5-7.
Natural variant2141Y → C in KECCR5-3B.
Natural variant2151S → L
Natural variant2231R → Q: dbSNP rs1800452.
Natural variant2281Missing
Natural variant2391T → S in INCCR5-71A.
Natural variant2461L → P in UGCCR5-145A.
Natural variant2881T → M in INCCR5-72A.
Natural variant3011G → V: dbSNP rs1800943.
Natural variant3021E → G in TZCCR5-179.
Natural variant3031K → E in THCCR5-5.
Natural variant3061N → S in MWCCR5-1567.
Natural variant3221K → R in THCCR5-5.
Natural variant3331E → G in THCCR5-2.
Natural variant3351A → V in MWCCR5-1567, MWCCR5-1568, ZWCCR5-14 and ZWCCR5-112. dbSNP rs1800944.
Natural variant3391Y → F in TZCCR5-181A and MWCCR5-107. dbSNP rs1800945.
Natural variant3451E → G in UGCCR5-145C.

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
Mutagenesis31Y → F: No sulfation and greatly decreases binding of CCL4 and CCL5; when associated with F-10; F-14 and F-15
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
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
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
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
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
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
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
Mutagenesis161T → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-17
Mutagenesis171S → A: Similar decrease in molecular mass when treated with O-glycosidase as for wild type; when associated with A-16
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
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
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
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
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
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
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

Secondary structure