CCL5 (C-C motif chemokine ligand 5)

Gene

• Entrez ID: 6352
• Gene name: C-C motif chemokine ligand 5
• Gene symbol: CCL5
• Synonyms: D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228, eoCP
• Chromosome: 17
• Chromosome location: 17q12
• Summary: This gene is one of several chemokine genes clustered on the q-arm of chromosome 17. Chemokines form a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of the N-terminal cysteine residues of the mature peptide. This chemokine, a member of the CC subfamily, functions as a chemoattractant for blood monocytes, memory T helper cells and eosinophils. It causes the release of histamine from basophils and activates eosinophils. This cytokine is one of the major HIV-suppressive factors produced by CD8+ cells. It functions as one of the natural ligands for the chemokine receptor chemokine (C-C motif) receptor 5 (CCR5), and it suppresses in vitro replication of the R5 strains of HIV-1, which use CCR5 as a coreceptor. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT005677	hsa-miR-98-5p	ELISA	20589685
MIRT005677	hsa-miR-98-5p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	26126865
MIRT005678	hsa-miR-125a-5p	ELISA	20589685
MIRT053786	hsa-miR-214-3p	ELISA, Immunohistochemistry, Luciferase reporter assay, qRT-PCR	23171795
MIRT437504	hsa-miR-146a-5p	Luciferase reporter assay	24996260
MIRT518342	hsa-miR-5089-5p	PAR-CLIP	23446348
MIRT518342	hsa-miR-5089-5p	HITS-CLIP	23313552
MIRT518343	hsa-miR-7151-3p	PAR-CLIP	23446348
MIRT518343	hsa-miR-7151-3p	HITS-CLIP	23313552
MIRT518344	hsa-miR-5095	PAR-CLIP	23446348
MIRT518344	hsa-miR-5095	HITS-CLIP	23313552
MIRT518345	hsa-miR-4775	PAR-CLIP	23446348
MIRT518346	hsa-miR-6508-3p	PAR-CLIP	23446348
MIRT518347	hsa-miR-4726-5p	PAR-CLIP	23446348
MIRT518348	hsa-miR-4640-5p	PAR-CLIP	23446348
MIRT518349	hsa-miR-6853-5p	PAR-CLIP	23446348
MIRT518350	hsa-miR-6506-5p	PAR-CLIP	23446348
MIRT518350	hsa-miR-6506-5p	HITS-CLIP	23313552
MIRT518351	hsa-miR-619-5p	PAR-CLIP	23446348
MIRT518351	hsa-miR-619-5p	HITS-CLIP	23313552
MIRT518352	hsa-miR-4735-5p	PAR-CLIP	23446348
MIRT518353	hsa-miR-6504-3p	PAR-CLIP	23446348
MIRT518353	hsa-miR-6504-3p	HITS-CLIP	23313552
MIRT518354	hsa-miR-4438	PAR-CLIP	23446348
MIRT518354	hsa-miR-4438	HITS-CLIP	23313552
MIRT518355	hsa-miR-590-3p	PAR-CLIP	23446348
MIRT685341	hsa-miR-6807-5p	HITS-CLIP	23313552
MIRT685342	hsa-miR-6720-5p	HITS-CLIP	23313552
MIRT685343	hsa-miR-6512-3p	HITS-CLIP	23313552
MIRT685344	hsa-miR-5589-5p	HITS-CLIP	23313552
MIRT685345	hsa-miR-4731-5p	HITS-CLIP	23313552
MIRT685346	hsa-miR-186-3p	HITS-CLIP	23313552
MIRT685347	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT685348	hsa-miR-520h	HITS-CLIP	23313552
MIRT685349	hsa-miR-520g-3p	HITS-CLIP	23313552
MIRT685350	hsa-miR-512-3p	HITS-CLIP	23313552
MIRT685351	hsa-miR-520e	HITS-CLIP	23313552
MIRT685352	hsa-miR-520d-3p	HITS-CLIP	23313552
MIRT685353	hsa-miR-520c-3p	HITS-CLIP	23313552
MIRT685354	hsa-miR-520b	HITS-CLIP	23313552
MIRT685355	hsa-miR-520a-3p	HITS-CLIP	23313552
MIRT685356	hsa-miR-373-3p	HITS-CLIP	23313552
MIRT685357	hsa-miR-372-3p	HITS-CLIP	23313552
MIRT685358	hsa-miR-302e	HITS-CLIP	23313552
MIRT685359	hsa-miR-302d-3p	HITS-CLIP	23313552
MIRT685360	hsa-miR-302c-3p	HITS-CLIP	23313552
MIRT685361	hsa-miR-302b-3p	HITS-CLIP	23313552
MIRT685362	hsa-miR-302a-3p	HITS-CLIP	23313552
MIRT685363	hsa-miR-93-5p	HITS-CLIP	23313552
MIRT685364	hsa-miR-526b-3p	HITS-CLIP	23313552
MIRT685365	hsa-miR-519d-3p	HITS-CLIP	23313552
MIRT685366	hsa-miR-20b-5p	HITS-CLIP	23313552
MIRT685367	hsa-miR-20a-5p	HITS-CLIP	23313552
MIRT685368	hsa-miR-17-5p	HITS-CLIP	23313552
MIRT685369	hsa-miR-106b-5p	HITS-CLIP	23313552
MIRT685370	hsa-miR-106a-5p	HITS-CLIP	23313552
MIRT732867	hsa-let-7g-3p	ELISA, Luciferase reporter assay, qRT-PCR, Western blot	26126865

Transcription factors

Transcription factor	Regulation	Reference
ATF3	Unknown	10760799
CREB1	Unknown	11413310
IRF1	Unknown	10385645
IRF3	Unknown	10385645;20483755
IRF7	Unknown	10385645
JUN	Unknown	11413310
JUND	Unknown	10760799
KLF13	Unknown	17513757;22797700
NFKB1	Activation	11478739;9120310
NFKB1	Unknown	11259372;11389171;11413310;12122011;19786024
NFKBIA	Repression	15228586
REL	Unknown	11259372
RELA	Activation	11478739;9120310
RELA	Unknown	11259372;11389171;11413310;12122011;19786024
SP1	Unknown	11259372
SPI1	Unknown	10760799

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	IMP	21147091
GO:0002407	Process	Dendritic cell chemotaxis	TAS	18337562
GO:0002548	Process	Monocyte chemotaxis	IBA	21873635
GO:0002548	Process	Monocyte chemotaxis	IC	10660125
GO:0002676	Process	Regulation of chronic inflammatory response	TAS	10488085
GO:0004435	Function	Phosphatidylinositol phospholipase C activity	IDA	10734056
GO:0004672	Function	Protein kinase activity	IDA	10734056
GO:0005515	Function	Protein binding	IPI	8699119, 23480650, 28381538
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0006468	Process	Protein phosphorylation	IEA
GO:0006816	Process	Calcium ion transport	IDA	10734056
GO:0006874	Process	Cellular calcium ion homeostasis	IDA	10734056
GO:0006887	Process	Exocytosis	IDA	10734056
GO:0006935	Process	Chemotaxis	NAS	1380064
GO:0006954	Process	Inflammatory response	IBA	21873635
GO:0006954	Process	Inflammatory response	IDA	21147091
GO:0007159	Process	Leukocyte cell-cell adhesion	IDA	8558019
GO:0007186	Process	G protein-coupled receptor signaling pathway	IBA	21873635
GO:0007186	Process	G protein-coupled receptor signaling pathway	IDA	17001303, 23979485
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS
GO:0007267	Process	Cell-cell signaling	IDA	8558019
GO:0008009	Function	Chemokine activity	IBA	21873635
GO:0008009	Function	Chemokine activity	IDA	1699135
GO:0008009	Function	Chemokine activity	NAS	7524281
GO:0009615	Process	Response to virus	TAS	10488085
GO:0009636	Process	Response to toxic substance	IDA	10841574
GO:0010536	Process	Positive regulation of activation of Janus kinase activity	TAS	11278738
GO:0010759	Process	Positive regulation of macrophage chemotaxis	IDA	16778803
GO:0010820	Process	Positive regulation of T cell chemotaxis	IBA	21873635
GO:0010820	Process	Positive regulation of T cell chemotaxis	IDA	1699135, 7544376, 16778803, 18337562
GO:0014068	Process	Positive regulation of phosphatidylinositol 3-kinase signaling	IDA	7544376
GO:0014911	Process	Positive regulation of smooth muscle cell migration	IDA	21297082
GO:0016004	Function	Phospholipase activator activity	IDA	10734056
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0030298	Function	Receptor signaling protein tyrosine kinase activator activity	IDA	10488085
GO:0030335	Process	Positive regulation of cell migration	IDA	7545673
GO:0030593	Process	Neutrophil chemotaxis	IBA	21873635
GO:0031328	Process	Positive regulation of cellular biosynthetic process	IDA	18337562
GO:0031584	Process	Activation of phospholipase D activity	IDA	9469451
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IDA	21147091
GO:0031726	Function	CCR1 chemokine receptor binding	IDA	10910894
GO:0031726	Function	CCR1 chemokine receptor binding	IPI	7545673, 8699119, 10660125, 10734056
GO:0031726	Function	CCR1 chemokine receptor binding	TAS	9417081
GO:0031729	Function	CCR4 chemokine receptor binding	TAS	9417081
GO:0031730	Function	CCR5 chemokine receptor binding	IPI	9139699
GO:0033634	Process	Positive regulation of cell-cell adhesion mediated by integrin	IDA	8558019
GO:0034112	Process	Positive regulation of homotypic cell-cell adhesion	IDA	10488085
GO:0042056	Function	Chemoattractant activity	IDA	15001559
GO:0042102	Process	Positive regulation of T cell proliferation	IDA	18832695
GO:0042119	Process	Neutrophil activation	IDA	10488085
GO:0042327	Process	Positive regulation of phosphorylation	IDA	18337562
GO:0042379	Function	Chemokine receptor binding	IPI	7517217, 9139699
GO:0042531	Process	Positive regulation of tyrosine phosphorylation of STAT protein	IDA	9417081
GO:0042802	Function	Identical protein binding	IPI	15530372, 21827949, 23480650, 28381538
GO:0042803	Function	Protein homodimerization activity	IDA	10488085
GO:0043491	Process	Protein kinase B signaling	IMP	21147091
GO:0043547	Process	Positive regulation of GTPase activity	IBA	21873635
GO:0043621	Function	Protein self-association	IDA	10488085
GO:0043922	Process	Negative regulation by host of viral transcription	IDA	10841574
GO:0044344	Process	Cellular response to fibroblast growth factor stimulus	IEP	9407497
GO:0045070	Process	Positive regulation of viral genome replication	TAS	10488085
GO:0045071	Process	Negative regulation of viral genome replication	IDA	10490959
GO:0045089	Process	Positive regulation of innate immune response	TAS	21148810
GO:0045744	Process	Negative regulation of G protein-coupled receptor signaling pathway	IDA	10734056
GO:0045785	Process	Positive regulation of cell adhesion	IDA	10910894
GO:0045948	Process	Positive regulation of translational initiation	NAS	18337562
GO:0046427	Process	Positive regulation of receptor signaling pathway via JAK-STAT	TAS	11278738
GO:0046817	Function	Chemokine receptor antagonist activity	IDA	8631850
GO:0048020	Function	CCR chemokine receptor binding	IBA	21873635
GO:0048245	Process	Eosinophil chemotaxis	IDA	16778803
GO:0048246	Process	Macrophage chemotaxis	TAS	18337562
GO:0048247	Process	Lymphocyte chemotaxis	IBA	21873635
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IDA	21297082
GO:0050796	Process	Regulation of insulin secretion	IDA	23979485
GO:0050863	Process	Regulation of T cell activation	IDA	10488085
GO:0050918	Process	Positive chemotaxis	IEA
GO:0051928	Process	Positive regulation of calcium ion transport	IDA	8699119
GO:0061098	Process	Positive regulation of protein tyrosine kinase activity	IEA
GO:0070098	Process	Chemokine-mediated signaling pathway	IBA	21873635
GO:0070098	Process	Chemokine-mediated signaling pathway	IDA	17001303
GO:0070098	Process	Chemokine-mediated signaling pathway	TAS	18337562
GO:0070100	Process	Negative regulation of chemokine-mediated signaling pathway	IEA
GO:0070233	Process	Negative regulation of T cell apoptotic process	IDA	10488085
GO:0070234	Process	Positive regulation of T cell apoptotic process	IDA	10488085
GO:0070374	Process	Positive regulation of ERK1 and ERK2 cascade	IBA	21873635
GO:0071346	Process	Cellular response to interferon-gamma	IBA	21873635
GO:0071346	Process	Cellular response to interferon-gamma	IEP	9407497
GO:0071347	Process	Cellular response to interleukin-1	IBA	21873635
GO:0071347	Process	Cellular response to interleukin-1	IEP	9407497
GO:0071356	Process	Cellular response to tumor necrosis factor	IBA	21873635
GO:0071356	Process	Cellular response to tumor necrosis factor	IEP	9407497
GO:0071407	Process	Cellular response to organic cyclic compound	IDA	21147091
GO:0090026	Process	Positive regulation of monocyte chemotaxis	IDA	1699135, 19779041
GO:1901214	Process	Regulation of neuron death	IDA	17001303
GO:2000406	Process	Positive regulation of T cell migration	IDA	23620790
GO:2000503	Process	Positive regulation of natural killer cell chemotaxis	IDA	7545673

Other IDs

• MIM: 187011
• HGNC: 10632
• e!Ensembl: ENSG00000271503

Protein

• UniProt ID: P13501
• Protein name: C-C motif chemokine 5 (EoCP) (Eosinophil chemotactic cytokine) (SIS-delta) (Small-inducible cytokine A5) (T cell-specific protein P228) (TCP228) (T-cell-specific protein RANTES) [Cleaved into: RANTES(3-68); RANTES(4-68)]
• Protein function: Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. May activate several chemokine receptors including CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils (PubMed:16791620, PubMed:1380064, PubMed:8525373, PubMed:9516414, PubMed:15923218). May also be an agonist of the G protein-coupled receptor GPR75, stimulating inositol trisphosphate production and calcium mobilization through its activation. Together with GPR75, may play a role in neuron survival through activation of a downstream signaling pathway involving the PI3, Akt and MAP kinases. By activating GPR75 may also play a role in insulin secretion by islet cells (PubMed:23979485).
• PDB: 1B3A, 1EQT, 1HRJ, 1RTN, 1RTO, 1U4L, 1U4M, 1U4P, 1U4R, 2L9H, 2VXW, 5CMD, 5COY, 5DNF, 5L2U, 5UIW, 6AEZ, 6C6D, 6FGP, 6LOG, 6STK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00048	IL8	31 → 88	Small cytokines (intecrine/chemokine), interleukin-8 like	Domain

• Sequence:

  MKVSAAALAVILIATALCAPASASPYSSDTTPCCFAYIARPLPRAHIKEYFYTSGKCSNP
  AVVFVTRKNRQVCANPEKKWVREYINSLEMS

• Sequence length: 91

Pathways

KEGG:

Cytokine-cytokine receptor interaction
Viral protein interaction with cytokine and cytokine receptor
Chemokine signaling pathway
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
Cytosolic DNA-sensing pathway
TNF signaling pathway
Prion disease
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Chagas disease
Human cytomegalovirus infection
Influenza A
Herpes simplex virus 1 infection
Rheumatoid arthritis
Lipid and atherosclerosis

Reactome:

Chemokine receptors bind chemokines
G alpha (i) signalling events
Interleukin-10 signaling

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Hyperoxaluria	Hyperoxaluria, Oxalosis	rs397509360, rs138207257, rs2041105506, rs267606763, rs267606764, rs80356708, rs119490108, rs121908520, rs121908521, rs121908522, rs121908523, rs121908524, rs121908525, rs121908526, rs121908527, rs121908528, rs121908530, rs121908529, rs180177201, rs180177238, rs180177321, rs672601351, rs180177322, rs180177157, rs180177168, rs180177195, rs180177197, rs180177207, rs180177227, rs180177239, rs180177253, rs180177259, rs786204545, rs180177267, rs180177301, rs180177156, rs180177307, rs-1, rs138584408, rs180177194, rs180177213, rs180177191, rs34116584, rs180177262, rs180177268, rs180177278, rs180177162, rs180177166, rs180177170, rs180177171, rs180177172, rs180177173, rs180177177, rs767586362, rs180177181, rs180177182, rs796052058, rs796052069, rs180177183, rs180177184, rs180177185, rs180177186, rs796052059, rs180177187, rs180177189, rs180177193, rs180177198, rs796052060, rs180177199, rs180177200, rs180177202, rs180177203, rs796052061, rs180177208, rs138025751, rs796052067, rs113681235, rs796052070, rs180177210, rs180177211, rs180177214, rs180177215, rs180177217, rs180177219, rs180177220, rs180177221, rs180177222, rs180177223, rs180177224, rs180177225, rs180177231, rs180177232, rs180177233, rs180177234, rs180177235, rs180177236, rs180177237, rs180177240, rs180177241, rs180177243, rs180177244, rs796052062, rs180177245, rs180177246, rs536352238, rs180177247, rs180177248, rs180177250, rs180177251, rs180177252, rs180177254, rs111996685, rs111742810, rs180177256, rs1553648931, rs180177257, rs180177258, rs180177261, rs796052072, rs180177263, rs180177264, rs180177265, rs796052068, rs180177269, rs180177270, rs180177272, rs180177273, rs180177276, rs180177279, rs180177284, rs180177281, rs180177286, rs180177285, rs180177287, rs180177288, rs180177292, rs180177293, rs180177294, rs180177295, rs180177296, rs180177297, rs180177298, rs796052063, rs180177299, rs796052074, rs180177300, rs180177302, rs796052064, rs180177303, rs180177155, rs756437332, rs796052065, rs180177158, rs180177160, rs180177161, rs180177163, rs180177164, rs796052066, rs180177255, rs180177289, rs796052077, rs180177311, rs180177319, rs180177304, rs180177305, rs796052078, rs796052081, rs180177308, rs180177309, rs180177313, rs180177314, rs180177315, rs180177316, rs796052082, rs180177317, rs180177324, rs180177325, rs746419489, rs764396564, rs758304537, rs796052084, rs796052088, rs796052089, rs150702945, rs767405535, rs796052090, rs202047589, rs185803104, rs796052085, rs755562733, rs796052086, rs770050262, rs756489804, rs796052087, rs149150736, rs777046879, rs796052091, rs796052092, rs1057516896, rs751101495, rs1057517398, rs1057517238, rs1057516299, rs1057517333, rs1057517026, rs771019056, rs1057516990, rs1057516292, rs1057516823, rs1057516831, rs1419840309, rs757796926, rs1553648568, rs778567956, rs112673831, rs1553649375, rs1553648488, rs1553648493, rs1553649007, rs1554746094, rs1244822375, rs1554746097, rs1554746565, rs1422977131, rs1331106064, rs1554746793, rs1257080057, rs1554748528, rs1554748598, rs777683624, rs776817346, rs779208888, rs1554747871, rs111256477, rs1554747933, rs1554748534, rs1554748574, rs1425736036, rs1554874130, rs1554874148, rs746776892, rs990830655, rs752277936, rs749315029, rs1564297234, rs1564753668, rs924232072, rs1564300888, rs1564760008, rs774654020, rs1588757756, rs148049120, rs1553648979, rs1822898131	16284884
Asthma	Asthma	rs324981, rs121912630, rs150116809, rs4950928, rs708494, rs1581842283	8534483
Glomerulonephritis	Glomerulonephritis	rs778043831	10385480
Pulmonary fibrosis	Pulmonary Fibrosis	rs121918666, rs199422300, rs121917737, rs121917834, rs199422294, rs201159197, rs199422297, rs199422305, rs751381953, rs876661305, rs878853260, rs863223336, rs786205702, rs1555811762, rs1060502990, rs1555903332, rs1554038539, rs1554042899, rs938938578	17620002
Dermatitis	Dermatitis, Atopic	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	18249437

Unknown
Disease name	Disease term	dbSNP ID	References
Alveolitis	Alveolitis, Fibrosing		17620002
Biliary cirrhosis	Biliary cirrhosis, Biliary Cirrhosis, Primary, 1, Primary biliary cirrhosis		12126966
Bright disease	Bright Disease		10385480
Autoimmune hepatitis	Autoimmune Chronic Hepatitis		21227906
Eczema	Eczema, Infantile		18249437
Malignant mesothelioma	Malignant mesothelioma		25162674
Biliary cholangitis	Secondary Biliary Cholangitis		12126966