Property Summary

NCBI Gene PubMed Count 72
PubMed Score 60.36
PubTator Score 313.89

Knowledge Summary

Patent (71,386)

TINX Plot

  Disease (5)

Expression

  Differential Expression (4)

Disease log2 FC p
medulloblastoma, large-cell 1.200 3.4e-04
lung carcinoma -1.100 3.7e-08
ovarian cancer 1.200 8.0e-11
psoriasis 1.500 2.3e-37

Protein-protein Interaction (180)

GNAT3   GRM8   CORT   CCL21   CXCL11   GRM6   CCL25   CCL16   ADCY6   GALR2   CXCL13   ADCY3   ADCY9   GALR3   GABBR2   S1PR2   ADCY5   S1PR4   C3   C5   KNG1   POMC   PENK   PDYN   PPY   NPY   PPBP   PF4   CXCL10   GNAI2   APP   GNAI3   CXCL1   SAA1   ADORA3   PYY   CXCL8   CCL5   DRD2   ADRA2C   GNAZ   CXCL2   CXCL3   PMCH   S1PR1   FPR1   DRD4   GAL   CXCR1   CXCR2   FPR3   FPR2   ACKR3   NPY1R   SSTR1   SSTR2   SSTR4   CCR7   CXCR5   SSTR3   SSTR5   OPRM1   DRD3   ADCY8   OPRD1   OPRK1   OPRL1   CCR2   CXCL5   PTGER3   CCR10   GALR1   MTNR1A   CXCL12   NPBWR1   NPBWR2   NMU   PIK3CG   HCAR3   NPY2R   MTNR1B   CXCR3   NPY4R   P2RY4   CCR5   CCR6   CCR8   CCR9   ADCY7   CCL23   TAS2R38   TAS2R39   TAS2R40   TAS2R41   TAS2R43   TAS2R31   TAS2R45   TAS2R46   TAS2R30   TAS2R19   TAS2R20   TAS2R50   TAS2R60   GNG2   CXCR4   SST   GNB1   GNAI1   CCL20   CXCL6   PLCB2   PLCB3   GNA12   CXCL9   ADCY2   ADCY1   GPR17   PNOC   GPR18   GNA13   GRM2   GRM7   GRM3   GRM4   P2RY14   NPY5R   NMS   PIK3R6   TAS2R42   MT-RNR2   NPW   ADCY4   NPB   HCAR2   OXER1   RXFP4   RLN3   PIK3R5   LPAR1   ARHGEF1   MCHR2   OXGR1   S1PR3   GPER1   MCHR1   CCL19   P2RY13   SUCNR1   HCAR1   NMUR2   LPAR5   S1PR5   P2RY12   CXCL16   HRH4   NMUR1   LPAR2   PLCB1   CCL28   HEBP1   RXFP3   TAS2R16   TAS2R14   TAS2R13   TAS2R10   TAS2R9   TAS2R8   TAS2R7   TAS2R5   TAS2R4   TAS2R3   TAS2R1   ARHGEF12   GABBR1   LPAR3   GPR55   CCL27   HRH3   INSL5   PTGDR2  

Gene RIF (62)

PMID Text
26847489 CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology.
26683175 CCL22-specific antibodies reveal that engagement of two distinct binding domains on CCL22 is required for CCR4-mediated function.
26093920 Distinctive Treg associated CCR4-CCL22 expression profile with altered frequency of Th17/Treg cell in the immunopathogenesis of Pemphigus Vulgaris.
25790118 Data show that CCR4 was over-expressed in lymph node-negative human gastric cancer tissues and suggest its involvement in promoting tumor invasion probably, through up-regulation of MMP9.
25488980 These findings implicate somatic gain-of-function CCR4 mutations in the pathogenesis of adult T cell leukemia/lymphoma.
25148803 CCR4 C1014T and CCL22 C16A genetic variations were neither associated with the risk, nor with the progression of colorectal cancer in Iranian population
25013801 Higher percentages of CCR4+ CD4 TEM cells in acute RSV infection were accompanied with higher percentages of CXCR3+ CD8 TEM cells, whereas the development of long-lived memory CXCR3+ CD4 and CD8 TCM cells seems to be compromised
24563252 Data show that CCR4 exists in at least two distinct conformations, which are differentially activated by ligand.
24554520 CCR4 has a role in tumor aggressive behavior in renal cell carcinoma
24127572 Anti-CCR4 monoclonal antibody treatment is instrumental for evoking and augmenting antitumor immunity in cancer patients by selectively depleting eTreg cells.
23731651 CCL17-induced, CCR4-dependent release of CGRP by human airway epithelial cells represents a novel inflammatory pathway in patients with asthma and allergic disease.
23649168 CCR4 mediates CCL17 induced cell migration via increased total RhoA and active RhoA protein levels in colon cancer cells.
23644599 Authors identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex.
23333304 HIV-1 Vif upregulates the expression of chemokine (C-C motif) receptor 4 (CCR4) in Vif-expression T cells
23180648 lymph node metastasis of CCR4(+) HNSCC is promoted by CCL22 in an autocrine or M2-like macrophage-dependent paracrine manner.
22842622 HIV-1 Vif upregulates the expression of chemokine (C-C motif) receptor 4 (CCR4) in Vif-expression T cells
22490506 CCR4+ memory T-cell frequency is increased in patients with Wegener's granulomatosis with polyangiitis.
21739422 CCR4-, CCR5-, CXCR3-, and selectin ligand-expressing CD4+ T cells preferentially accumulate in the joints of children with juvenile idiopathic arthritis.
21525208 A high amino acid charge of the envelope glycoprotein 120 V3 region is important for binding to host CXCR4 receptor.
21443538 aberrant expression of CCR4 in human gastric cancer could contribute to tumor-induced immunosuppression.
20963786 high-level lineage-independent induction of CCR4 can occur following T-cell activation without accessibility-associated changes in histone H3, but that without such changes expression is transient rather than persistent.
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20438785 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20412707 CD4+CD25high Treg cells of Wegener granulomatosis-patients exhibited decreased numbers of cells co-expressing FoxP3 and CCR4
20406964 Observational study of gene-disease association. (HuGE Navigator)
20364559 data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure.
20334681 We suggest that CCR4 and CCR6 expression on CD4(+) T cells should be considered as markers of disease activity in systemic lupus erythematosus.
20237496 Observational study of gene-disease association. (HuGE Navigator)
20237293 CCR4 might play a role in allergen-driven T helper type (Th)2 cell accumulation in asthmatic airways.
20164417 CCR4 ligands secreted by dendritic cells recruit regulatory T cells (Tregs) to sites of inflammation in patients with autoimmune and chronic hepatitis.
20148806 Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses.
19942450 Data show that MDC/CCL22 is present in the synovial membrane of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients and in synovial fluid of patients with RA and PsA, which would enable migration of CCR4 expressing memory cells.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19903885 Data show that TH treatment promoted rapid and sustained hCCR4 recruitment to the TH-responsive deiodinase 1 promoter and TR co-localizes with hCCR4 in the nucleus and interacts with hCCR4 in 2-hybrid and pull-down assays.
19423540 Observational study of gene-disease association. (HuGE Navigator)
19374191 CCR4, a chemokine receptor known to be selectively expressed by T cell subsets such as Th2 cells, skin-homing memory/effector T cells, and regulatory T cells. (review)
19261691 CCR4 was expressed on a part of the memory cell population and CCR4+CD8+ memory T cells had the ability to produce multiple cytokines including IL-4 and to migrate in response to CC chemokine receptor ligand (CCL)17/TARC and CCL22/MDC.
19244125 Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome.
19239991 provide further dynamic evidence, in line with the multistep cascade paradigm for leukocyte transendothelial migration, to support a critical role for CCR4 in cutaneous T-cell lymphoma migration
19106589 ratio of CCR4+/CXCR3+ cells was 4.45 in chemotherapy and 0.72 in immunotherapy
18782672 CCR4 and CCR10 are expressed on epidermal keratinocytes and that both are functional in terms of skin cytokine production and/or migration to their ligand CCL17 and CCL27, respectively.
18071306 aberrantly expressed Fra-2 in association with JunD may play a major role in CCR4 expression and oncogenesis in adult T-cell leukemia.
17546636 Bexarotene reduces CCR4-positive lymphocytes.
17117949 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
17071491 CCR4 and CCR10 may play an important role in ATLL invasion into the skin
15955100 CCR4 and TARC/CCL17 play role in pathophysiology of cutaneous lupus erythematosus(CLE). Cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.
15857508 HIV-1 Vif upregulates the expression of chemokine (C-C motif) receptor 4 (CCR4) in Vif-expression T cells
15621800 review of possible relationship of CCR4 role in T cell migration and skin infiltration in ATL, and of selective expression of CCR4 by Th2 and regulatory T cells and possible origin of ATL in Th2 or regulatory T cells.
15569983 CC chemokine receptor 4 has a role in adult T-Cell leukemia/lymphoma
15328188 CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas.
15202833 Observational study of gene-disease association. (HuGE Navigator)
15187160 although there is PI(3,4,5)P(3) accumulation downstream of CCR4, phosphoinositide 3-kinase activity is a dispensable signal for CCR4-stimulated chemotaxis of Th2 cells and the CEM T cell line.
14657875 airway allergen-specific T(H)2 cells are CCR4(+), but in the atopic child CCR4 does not distinguish between recall antigen and allergen specificity
12778466 Increased expression of CCR4, which is proposed to guide CD25(+) Ts cells to DC, is an intrinsic feature of CD25(+) Ts cells.
12485447 In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals.
12456591 CCR4+ cells were present predominantly in the lesional skin of atopic dermatitis patients, but not in the non-lesional skin
12429730 HIV-1 Vif upregulates the expression of chemokine (C-C motif) receptor 4 (CCR4) in Vif-expression T cells
12406880 The skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4.
12270118 Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors
12070001 CCR4 is mainly expressed by a high cytokine (interleukin-4/interleukin-2)-producing (CD4) subset of natural killer t-cells.
11861261 CCR4 is expressed with high frequency in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells and in ATL skin lesions.
8884276 The human CCR4 gene is localized at Chr 3p24.

AA Sequence

MNPTDIADTTLDESIYSNYYLYESIPKPCTKEGIKAFGELFLPPLYSLVFVFGLLGNSVVVLVLFKYKRL      1 - 70
RSMTDVYLLNLAISDLLFVFSLPFWGYYAADQWVFGLGLCKMISWMYLVGFYSGIFFVMLMSIDRYLAIV     71 - 140
HAVFSLRARTLTYGVITSLATWSVAVFASLPGFLFSTCYTERNHTYCKTKYSLNSTTWKVLSSLEINILG    141 - 210
LVIPLGIMLFCYSMIIRTLQHCKNEKKNKAVKMIFAVVVLFLGFWTPYNIVLFLETLVELEVLQDCTFER    211 - 280
YLDYAIQATETLAFVHCCLNPIIYFFLGEKFRKYILQLFKTCRGLFVLCQYCGLLQIYSADTPSSSYTQS    281 - 350
TMDHDLHDAL                                                                351 - 360
//

Text Mined References (73)

PMID Year Title
26847489 2016 CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis.
26683175 2015 CCL22-specific Antibodies Reveal That Engagement of Two Distinct Binding Domains on CCL22 Is Required for CCR4-mediated Function.
26093920 2015 Distinctive Treg associated CCR4-CCL22 expression profile with altered frequency of Th17/Treg cell in the immunopathogenesis of Pemphigus Vulgaris.
25790118 2015 Aberrant CCR4 expression is involved in tumor invasion of lymph node-negative human gastric cancer.
25488980 2014 Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma.
25148803 2014 CCR4 C1014T and CCL22 C16A genetic variations in the Iranian patients with colorectal adenocarcinoma.
25013801 2014 The increased type-1 and type-2 chemokine levels in children with acute RSV infection alter the development of adaptive immune responses.
24563252 2014 Distinct conformations of the chemokine receptor CCR4 with implications for its targeting in allergy.
24554520 2014 Expression of chemokine receptor 4 was associated with poor survival in renal cell carcinoma.
24127572 2013 Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans.
23731651 2013 CCL17/thymus and activation-regulated chemokine induces calcitonin gene-related peptide in human airway epithelial cells through CCR4.
23649168 2013 CCR4 mediates CCL17 (TARC)-induced migration of human colon cancer cells via RhoA/Rho-kinase signaling.
23644599 2013 Structural basis for the recruitment of the human CCR4-NOT deadenylase complex by tristetraprolin.
23180648 2013 Autocrine and paracrine loops between cancer cells and macrophages promote lymph node metastasis via CCR4/CCL22 in head and neck squamous cell carcinoma.
22490506 2012 Increased frequency of CCR4+ and CCR6+ memory T-cells including CCR7+CD45RAmed very early memory cells in granulomatosis with polyangiitis (Wegener's).
21739422 2011 Coexpression of chemokine receptors CCR5, CXCR3, and CCR4 and ligands for P- and E-selectin on T lymphocytes of patients with juvenile idiopathic arthritis.
21525208 2011 Charged amino acid patterns of coreceptor use in the major subtypes of human immunodeficiency virus type 1.
21443538 2011 Aberrant expression of chemokine receptor CCR4 in human gastric cancer contributes to tumor-induced immunosuppression.
20963786 2010 Changes in histone acetylation and methylation that are important for persistent but not transient expression of CCR4 in human CD4+ T cells.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20438785 2010 Polymorphisms in innate immunity genes and risk of childhood leukemia.
20412707 Lower numbers of FoxP3 and CCR4 co-expressing cells in an elevated subpopulation of CD4+CD25high regulatory T cells from Wegener's granulomatosis.
20406964 2010 Risk of meningioma and common variation in genes related to innate immunity.
20364559 2010 Differential expression of Th2 chemokine receptors on T cells from atopic and nonatopic asthmatics in response to Der p 1-pulsed dendritic cells.
20334681 2010 Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus.
20237496 2010 New genetic associations detected in a host response study to hepatitis B vaccine.
20237293 2010 Chemokine receptor 4 plays a key role in T cell recruitment into the airways of asthmatic patients.
20190752 2010 Multiple common variants for celiac disease influencing immune gene expression.
20164417 2010 Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver.
20148806 2010 CC chemokine receptor 4 (CCR4) in human allergen-induced late nasal responses.
19942450 2010 Expression of MDC/CCL22 and its receptor CCR4 in rheumatoid arthritis, psoriatic arthritis and osteoarthritis.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19903885 2009 Identification of CCR4 and other essential thyroid hormone receptor co-activators by modified yeast synthetic genetic array analysis.
19423540 2009 Common variation in genes related to innate immunity and risk of adult glioma.
19374191 2008 [CCR4, HTLV-1 infection, and ATL oncogenesis].
19261691 2009 Human memory CCR4+CD8+ T cell subset has the ability to produce multiple cytokines.
19244125 2009 Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome.
19239991 2008 Differential CCR4 expression and function in cutaneous T-cell lymphoma cell lines.
19106589 2008 [The analysis of CCR4+/CXCR3+ cell ratio in gastrointestinal cancer patients receiving chemotherapy or immunotherapy].
18782672 2008 CCR4 and CCR10 are expressed on epidermal keratinocytes and are involved in cutaneous immune reaction.
18577758 2008 Dissociation of heterotrimeric g proteins in cells.
18240029 2008 Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors.
18071306 2008 Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia.
17546636 2007 Bexarotene blunts malignant T-cell chemotaxis in Sezary syndrome: reduction of chemokine receptor 4-positive lymphocytes and decreased chemotaxis to thymus and activation-regulated chemokine.
17117949 2006 Association screen for atopic dermatitis candidate gene regions using microsatellite markers in pooled DNA samples.
17071491 2006 Survey of chemokine receptor expression reveals frequent co-expression of skin-homing CCR4 and CCR10 in adult T-cell leukemia/lymphoma.
16137713 2006 Chemokine-like factor 1 is a functional ligand for CC chemokine receptor 4 (CCR4).
15955100 2005 Role of the chemokine receptor CCR4 and its ligand thymus- and activation-regulated chemokine/CCL17 for lymphocyte recruitment in cutaneous lupus erythematosus.
15621800 2005 Expression of CCR4 in adult T-cell leukemia.
15569983 2004 The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15328188 2004 CXC chemokine receptor 3 and CC chemokine receptor 4 expression in T-cell and NK-cell lymphomas with special reference to clinicopathological significance for peripheral T-cell lymphoma, unspecified.
15202833 2004 Lack of association of CCR4 single nucleotide polymorphism with atopic dermatitis in Japanese patients.
15187160 2004 Activation of phosphoinositide 3-kinases by the CCR4 ligand macrophage-derived chemokine is a dispensable signal for T lymphocyte chemotaxis.
14657875 2003 Adenoid-derived TH2 cells reactive to allergen and recall antigen express CC chemokine receptor 4.
12778466 2003 Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+CD25+ suppressor T cells.
12485447 2002 Increased CCR4 expression in cutaneous T cell lymphoma.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12456591 2002 Preferential expression of T(h)2-type chemokine and its receptor in atopic dermatitis.
12406880 2003 CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking.
12270118 2002 Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors CCR1 and CCR4.
12070001 2002 Trafficking machinery of NKT cells: shared and differential chemokine receptor expression among V alpha 24(+)V beta 11(+) NKT cell subsets with distinct cytokine-producing capacity.
11196669 1999 New variations of human CC-chemokine receptors CCR3 and CCR4.
10754297 2000 Human NK cells express CC chemokine receptors 4 and 8 and respond to thymus and activation-regulated chemokine, macrophage-derived chemokine, and I-309.
10466728 1999 The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells.
10036181 1999 Discovery of three novel orphan G-protein-coupled receptors.
9933589 1999 Truncation of macrophage-derived chemokine by CD26/ dipeptidyl-peptidase IV beyond its predicted cleavage site affects chemotactic activity and CC chemokine receptor 4 interaction.
9743322 1998 Enhanced anti-HIV-1 activity and altered chemotactic potency of NH2-terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor.
9430724 1998 Macrophage-derived chemokine is a functional ligand for the CC chemokine receptor 4.
9169480 1997 The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4.
8884276 1996 The genes encoding the human CC-chemokine receptors CC-CKR1 to CC-CKR5 (CMKBR1-CMKBR5) are clustered in the p21.3-p24 region of chromosome 3.
8573157 1996 Molecular cloning of murine CC CKR-4 and high affinity binding of chemokines to murine and human CC CKR-4.
7642634 1995 Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line.