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MGP000600

UniProt Annotations

Entry Information
Gene Namechemokine (C-C motif) receptor 5 (gene/pseudogene)
Protein EntryCCR5_HUMAN
UniProt IDP51681
SpeciesHuman
Comments
Comment typeDescription
DiseaseDiabetes 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. {ECO:0000269|PubMed:19073967}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
FunctionReceptor 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. {ECO:0000269|PubMed:11323418, ECO:0000269|PubMed:8639485, ECO:0000269|PubMed:8649511, ECO:0000269|PubMed:8649512, ECO:0000269|PubMed:8663314, ECO:0000269|PubMed:8699119}.
InteractionP13236:CCL4; NbExp=2; IntAct=EBI-489374, EBI-6625160; P13501:CCL5; NbExp=4; IntAct=EBI-489374, EBI-2848366;
PolymorphismSer-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.
PolymorphismVariations 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.
PolymorphismVariations in CCR5 are associated with susceptibility to West Nile virus (WNV) infection [MIM:610379].
PtmO-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. {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580}.
PtmPalmitoylation in the C-terminal is important for cell surface expression, and to a lesser extent, for HIV entry. {ECO:0000269|PubMed:11323418}.
PtmPhosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES. {ECO:0000269|PubMed:10085131}.
PtmSulfated 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. {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580, ECO:0000269|PubMed:21763489}.
SimilarityBelongs to the G-protein coupled receptor 1 family. {ECO:0000255|PROSITE-ProRule:PRU00521}.
Subcellular LocationCell membrane {ECO:0000269|PubMed:11323418}; Multi-pass membrane protein {ECO:0000269|PubMed:11323418}.
SubunitInteracts 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. {ECO:0000269|PubMed:10085131, ECO:0000269|PubMed:11448957, ECO:0000269|PubMed:11733580, ECO:0000269|PubMed:15757671, ECO:0000269|PubMed:16144840, ECO:0000269|PubMed:21763489, ECO:0000269|PubMed:22496149, ECO:0000269|PubMed:8663314, ECO:0000269|PubMed:8699119, ECO:0000269|PubMed:9632396}.
Tissue SpecificityHighly 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. {ECO:0000269|PubMed:8639485, ECO:0000269|PubMed:8663314}.
Web ResourceName=Wikipedia; Note=CC chemokine receptors entry; URL="http://en.wikipedia.org/wiki/CC_chemokine_receptors";
Web ResourceName=Wikipedia; Note=CCR5 receptor entry; URL="http://en.wikipedia.org/wiki/CCR5";
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