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CCR-4 Membrane Protein Introduction

Introduction of CCR-4

CCR-4 (designated CD194), which belongs to the G-protein-coupled receptor family, is encoded by the CCR4 gene. It is a receptor for the CC chemokine including CCL2 (MCP-1), CCL4 (MIP-1), CCL5 (RANTES), CCL17 (TARC), and CCL22 (Macrophage-derived chemokine). CCR4 is often expressed on leukemic cells in cutaneous T-cell lymphoma (CTCL). And it was indicated to be predominantly expressed by medullary CD4-single positive thymocytes expressing CD30, supporting its possible role in negative selection.

Basic Information of CCR-4
Protein Name C-C chemokine receptor type 4
Gene Name CCR4
Aliases K5-5, CD194, CC-CKR-4
Organism Homo sapiens (Human)
UniProt ID P51679
Transmembrane Times 7
Length (aa) 360
Sequence MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGELFLPPLYSLVFVFGLLGNSVVVLVLFKYKRL
RSMTDVYLLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMISWMYLVGFYSGIFFVMLMSIDRYLAIV
HAVFSLRARTLTYGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKTKYSLNSTTWKVLSSLEINILG
LVIPLGIMLFCYSMIIRTLQHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETLVELEVLQDCTFER
YLDYAIQATETLAFVHCCLNPIIYFFLGEKFRKYILQLFKTCRGLFVLCQYCGLLQIYSADTPSSSYTQS
TMDHDLHDAL

Function of CCR-4 Membrane Protein

Chemokines, act as the ligands of CCR-4, are a series of small polypeptide (approximately 8 to 14 kD), structurally related molecules that modulate cell trafficking of various types of leukocytes. The chemokines also play essential roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system (CNS) as well as on endothelial cells implicated in angiogenesis or angiostasis. The activity of CCR-4 is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. The importance of CCR4 and its ligand in allergic diseases has been fully proved by both human clinical samples and mouse disease models. The pivotal role of CCR-4 in skin-homing T cells has also been reported. This receptor can act as a chemoattractant homing receptor on circulating memory lymphocytes, as well as a coreceptor for some primary HIV-2 isolates. What’s more, it could mediate hippocampal-neuron survival in the CNS.

CCR 4 Membrane Protein Introduction

Application of CCR-4 Membrane Protein in Literature

1. DeFea K. Arresting CCR4: A New Look at an Old Approach to Combating Asthma. Am J Respir Cell Mol Biol. 2018, 58(6): 673-675. PubMed ID: 29856260

This article suggests that CCR4 is an enticing target for the treatment of asthma since it is important for recruitment of Th2 cells to the airway and its levels are increased on T cells of patients with asthma.

2. Dai J., et al. Potential Association of Anti-CCR4 Antibody Mogamulizumab and Graft-vs-Host Disease in Patients With Mycosis Fungoides and Sézary Syndrome. JAMA Dermatol. 2018, 154(6): 728-730. PubMed ID: 29800117

The author of this article evaluates the use of an anti-CCR4 antibody in patients prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT).

3. Fuji S. Role of anti-CCR4 antibody in the treatment of transplant-eligible patients with aggressive adult T-cell leukemia/lymphoma. Rinsho Ketsueki. 2018, 59(4): 426-431. PubMed ID: 29743403

The paper reveals that pre-transplant Moga (Mogamulizumab) was significantly associated with an increased risk of GVHD-related mortality, which supports the relevance of CCR4-expressing Tregs after allo-HSCT in humans.

4. Berlato C., et al. A CCR4 antagonist reverses the tumor-promoting microenvironment of renal cancer. J Clin Invest. 2017, 127(3): 801-813. PubMed ID: 28134623

This article demonstrated that the anti-CCR4 antibody, alone or in combination with other immune modulators, is a potential treatment approach to human solid cancers with high levels of CCR4-expressing tumor-infiltrating leukocytes and abnormal plasma CCR4 ligand levels.

5. Ou B., et al. CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer. Oncotarget. 2016, 7(30): 47637-47649. PubMed ID: 27356745

The investigations of this article showed that CCR4 might be implicated in TNF-α-regulated cancer cells metastasis and the combination of CCR4 and TNF-α is a more powerful prognostic marker for CRC patients, which indicated that CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis.

CCR-4 Preparation Options

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