C-C chemokine receptor type 5 selections

C-C chemokine receptor type 5; C-C CKR-5; CC-CKR-5; CCR-5; CCR5; HIV-1 fusion coreceptor; CHEMR13; sCD195 (CCR5, CMKBR5)

Function: - receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta & RANTES - transduces a signal by increasing the intracellular Ca⁺² - may play a role in the control of granulocytic lineage proliferation or differentiation - interacts with PRAF2 - efficient ligand binding to CCL3/MIP-1alpha & CCR4/MIP-1beta requires sulfation, O-glycosylation & sialic acid modifications - interacts with ADRBK1 - phosphorylation on Ser in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES Structure: - glycosylation on Ser-6 is required for efficient - sulfated on at least 2 of the N-terminal tTyr binding of CCL4. - sulfation is required for efficient binding of chemokines, CCL3 & CCL4 - O-glycosylated, but not N-glycosylated; Ser-6 appears to be the major site - Thr-16 & Ser-17 may also be glycosylated - also sialylated glycans present which contribute to chemokine binding - palmitoylation in the C-terminal is important for cell surface expression - belongs to the G-protein coupled receptor 1 family Compartment: cell membrane Expression: - expressed in spleen, thymus, in myeloid cell line THP-1, in promyeloblastic cell line KG-1A & on CD4+ & CD8+ T-cells > peripheral blood leukocytes, small intestine > ovary & lung Pathology: - coreceptor for HIV-1 (CD4 is primary receptor) - interacts with HIV-1 surface protein gp120 - sulfation contributes to the efficiency of HIV-1 entry - palmitoylation in the C-terminal may have role in HIV entry Pharmacology: - maraviroc (Selzentry) binds to CCR5 inhibiting entry of HIV1 into cells Polymorphism: - variations in CCR5 are associated with susceptibility or resistance to HIV1 - Ser-60 variant (in 1st intracellular domain of CCR5) results in diminished amounts in the membrane & thus diminished susceptibility to infection by microbes that depend on CCR5 as their receptors - variations in CCR5 are associated with susceptibility to West Nile virus

Interactions

molecular events

General

CC chemokine receptor cluster-of-differentiation antigen; cluster designation antigen; CD antigen phosphoprotein

Properties

SIZE: entity length = 352 aa MW = 41 kD COMPARTMENT: plasma membrane MOTIF: exoplasmic domain {1-30} MOTIF: Ser glycosylation site {S6} Ser glycosylation site {S7} Thr glycosylation site {T16} Ser glycosylation site {S17} transmembrane domain {31-58} cytoplasmic loop {59-68} transmembrane domain {69-89} exoplasmic loop {90-102} MOTIF: cysteine residue {C101} MODIFICATION: cysteine residue {C178} transmembrane domain {103-124} cytoplasmic loop {125-141} transmembrane domain {142-166} exoplasmic loop {167-198} MOTIF: cysteine residue {C178} MODIFICATION: cysteine residue {C101} transmembrane domain {199-218} cytoplasmic loop {219-235} transmembrane domain {236-260} exoplasmic loop {261-277} transmembrane domain {278-301} cytoplasmic domain {302-352} MOTIF: cysteine residue {C321} MODIFICATION: palmitate COMPARTMENT: membrane cysteine residue {C323} MODIFICATION: palmitate COMPARTMENT: membrane cysteine residue {C324} MODIFICATION: palmitate COMPARTMENT: membrane Ser phosphorylation site {S336} Ser phosphorylation site {S337} Ser phosphorylation site {S342} Ser phosphorylation site {S349}

Database Correlations

OMIM correlations UniProt P51681 Pfam PF00001 Entrez Gene 1234 KEGG correlations

References

UniProt :accession P51681
Wikipedia; CC chemokine receptors entry http://en.wikipedia.org/wiki/CC_chemokine_receptors
Wikipedia; CCR5 receptor entry http://en.wikipedia.org/wiki/CCR5

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