CCR5

CCR5 (C-C Motif Chemokine Receptor 5 (Gene/Pseudogene)) is a Protein Coding gene. Diseases associated with CCR5 include West Nile Virus and Diabetes Mellitus, Insulin-Dependent, 22. Among its related pathways are Cytokine Signaling in Immune system and Akt Signaling. Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity and phosphatidylinositol phospholipase C activity. An important paralog of this gene is CCR2.

Full Name

C-C Motif Chemokine Receptor 5 (Gene/Pseudogene)

Alternative Names

C-C Motif Chemokine Receptor 5 (Gene/Pseudogene); Chemokine (C-C Motif) Receptor 5; HIV-1 Fusion Coreceptor; CC-CKR-5; ChemR13; CMKBR5; CCR-5; Chemokine (C-C Motif) Receptor 5 (Gene/Pseudogene); C-C Motif Chemokine Receptor 5 A159A; Chemokine Recptor CCR5 Delta32;

Function

Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/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. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor (PubMed:30713770).
(Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.

Biological Process

Calcium ion transport Source: UniProtKB
Calcium-mediated signaling Source: UniProtKB
Cell-cell signaling Source: UniProtKB
Cell chemotaxis Source: GO_Central
Cell surface receptor signaling pathway Source: ProtInc
Cellular defense response Source: ProtInc
Cellular response to lipopolysaccharide Source: UniProtKB
Chemotaxis Source: ProtInc
Cytokine-mediated signaling pathway Source: Reactome
Dendritic cell chemotaxis Source: BHF-UCL
Entry into host Source: Reactome
Fusion of virus membrane with host plasma membrane Source: Reactome
G protein-coupled receptor signaling pathway Source: UniProtKB
Immune response Source: GO_Central
Inflammatory response Source: GO_Central
MAPK cascade Source: UniProtKB
Positive regulation of cytosolic calcium ion concentration Source: GO_Central
Release of sequestered calcium ion into cytosol by sarcoplasmic reticulum Source: UniProtKB
Response to cholesterol Source: UniProtKB
Signaling Source: UniProtKB

Cellular Location

Cell membrane

Involvement in disease

Diabetes mellitus, insulin-dependent, 22 (IDDM22): 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.

Topology

Extracellular: 1-30
Helical: 31-58
Cytoplasmic: 59-68
Helical: 69-89
Extracellular: 90-102
Helical: 103-124
Cytoplasmic: 125-141
Helical: 142-166
Extracellular: 167-198
Helical: 199-218
Cytoplasmic: 219-235
Helical: 236-260
Extracellular: 261-277
Helical: 278-301
Cytoplasmic: 302-352

PTM

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.