CD195 CCR5 (chemokine [C-C motif] receptor 5) (*See available information under CD CKR), CKR5
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 3 glycoprotein, 7 span
Peripheral blood
Thymocyte
Monocyte
T Cell
Leukocyte
Macrophage
Lymphocyte
Dendritic Cell
Astrocyte
Fibroblast
Promyelocyte
Langerhans Cell
Endothelial Cell
Muscle, Smooth
Epithelium
Hematopoietic Progenitor Cell
37 / 37

Expression
CD195 is expressed on leukocytes including blood lymphocytes, monocytes, macrophages and immature dendritic cells.   Among T cells, CD195 is expressed preferentially on a subset with the phenotype of activated memory cells the Th1 function.  CD195 is expressed at low levels on freshly isolated peripheral blood monocytes and T cells but can be upregulated by culturing monocytes in vitro and by prolonged stimulation of T cells in culture with IL-2, mitogens and other stimuli.  CD195 has been detected in Th1 type inflammation in vitro in synovial fluid from patients with rheumatoid arthritis.  Expression was found on CD4+ and CD8+ thymocytes, Langerhans cells, peripheral blood derived dendritic cells, hematopoietic progenitor cells and microglial cells.  It is expressed on neurons, astrocytes, leukocytes, capillary endothelial cells, epithelium, vascular smooth muscle and fibroblasts.  T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues express CD195 and CD184 in vivo but follicular dendritic cells in lymph nodes express neither, suggesting that trapping by these cells does not involve the major HIV co-receptors.  CD195 is found in promyelocytic cells.

Structure
MOLECULAR FAMILY NAME: Belongs to the chemokine receptor family.

CD195 is a multi-pass type-3 7 span 352 aa transmembrane glycoprotein.  It lacks a signal peptide but has a extracellular domain which contains a 30 aa N-terminal, a 50 aa C-terminus, O-linked intracellular hydrate and sulphate tyrosine amino acids, 7 hydrophobic putative transmembrane spanning domains and a cytoplasmic carboxyl terminal domain.  There are 3 short intracellular loops and 3 short extracellular loops.  CD195 is a chemokine receptor which are G-protein coupled receptors which forms a division of the leukocyte chemoattractant subfamily which is part of the rhodopsin family of GPCRs and it is the most closely related to CD192 (CCR2).  Human CD195 is a plasma membrane associated protein.

MOLECULAR MASS
CellType Unreduced Reduced
45 kDa

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION

CD195 undergoes O-glycosylation and sulphation of N-terminal tyrosine.  The latter is important for HIV co-receptor activity.  N-linked glycosylation of a potential site at 268 aa has not been demonstrated.  In the mouse, CD195 is 354 aa long and is 76% identical to the human CCR5 at the aa level.


Ligands
CD195 binds chemokines CCl3 (MIP-1α), CCL4 (MIP-1β), and CCL5 (RANTES) with high affinity.  It also binds with lower affinity CCL11 (eotaxin), CCR7 (MCP-3) and CCL13 (MCP-4).  It is also a coreceptor for HIV.

LIGANDS AND MOLECULES ASSOCIATED WITH CD195
Molecule Comment
MIP1a P form binds with higher affinity than the S form
RANTES
MIP1b This is only selective for CD195
MCP-2


Function
CD195 is a receptor for a C-C type chemokine.  Chemokine receptors mediate the function of chemokines which have roles as inducers of cell movements and activation.  CD195 is involved in regulating both innnate and adaptive immune responses.  It binds to MIP-1α, MIP-1β and RANTES and subsequently transduces a signal by increasing the intracellular calcium ions level.  Expression of CD195 was detected in a promyeloblastic cell line suggesting that it may play a role in the control of granulocytic lineage proliferation and differentiation.  Ligation of CD195 induces downstream signaling, including calcium flux and chemotaxis.  Knockout mice are healthly but they show deficits in handing infections and an increase in delayed hypersensitivity and antibody production, suggesting CD195 regulates the immune function in a complex way. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD195 IN INTACT ANIMAL

CD195 is a coreceptor for HIV-1 and has a susceptibility or resistance to HIV infection and variations in the CD195 gene influences the rate of progression to AIDS after infection.  Some individuals with an allele of CD195, which does not bind HIV, are resistant to infection.  CD195 regulates innate and adaptive immune responses and chemotaxis activation and transendothelial migration during inflammation and neutralizes HIV infection which is the key host factor responsible for HIV pathogenesis.  The HIV co-receptor activity of CD195 requires co-expression of CD4.  Both proteins bind to specific regions of the HIV envelope glycoprotein gp120 and evidence indicates that they may intereact physically even in the absence of gp120.



Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD195: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD195: No information



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 1234P51681
MouseP51682
Antibodies
2D7/CCR5   View Reactivity
3A9   View Reactivity

Revised June 25, 2008


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