Gene Report

Basic Information

Approved Symbol	CCL2
Approved Name	chemokine (C-C motif) ligand 2
Previous Symbol	SCYA2
Previous Name	"small inducible cytokine A2 (monocyte chemotactic protein 1, homologous to mouse Sig-je)"
Symbol Alias	MCP1, MCP-1, MCAF, SMC-CF, GDCF-2, HC11, MGC9434
Name Alias	"monocyte chemotactic protein 1, homologous to mouse Sig-je", "monocyte chemoattractant protein-1", "monocyte chemotactic and activating factor", "monocyte secretory protein JE", "small inducible cytokine subfamily A (Cys-Cys), member 2"
Location	17q11.2-q21.1
Position	chr17:32583847-32584222 (+)
External Links	Entrez Gene: 6347 Ensembl: ENSG00000108691 UCSC: uc002hhy.3 HGNC ID: 10618
No. of Studies (Positive/Negative)	3(2/1)
Type	Literature-origin; Protein mapped

Positive relationships between CCL2 and MDD (count: 2)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MCP1	Pae, 2004	patients and normal controls		We found significant differences in genotype and allele freq...... We found significant differences in genotype and allele frequencies. More...
CCL2	Carvalho LA, 2014	patients and normal controls	FC=1.1; P-value=0.018	Thirty-four of the 47 monocyte inflammatory-related genes w...... Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls More...

Positive relationships between CCL2 and other components at different levels (count: 0)

Positive relationship network of CCL2 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between CCL2 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
MCP-1	Altamura AC, 2010	Patients and nomal controls	chi(2) = 8.215; d.f. = 6; p = 0.223	No genotypic (chi(2) = 8.215, d.f. = 6, p = 0.223) or alleli...... No genotypic (chi(2) = 8.215, d.f. = 6, p = 0.223) or allelic (chi(2) = 5.058, d.f. = 3, p = 0.168) association for the A-2518G polymorphism of SCYA2 was found considering cases and controls. More...

Negative relationships between CCL2 and other components at different levels (count: 0)

CCL2 related SNPs in MK4MDD (count: 0)

CCL2 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
C-C motif chemokine 2	P13500	2(1/1)	Literature-origin

CCL2 related GO terms (count: 102)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0032869	cellular response to insulin stimulus	biological process	IEA
GO:0000165	MAPK cascade	biological process	IMP[21147091]
GO:0043491	protein kinase B signaling	biological process	IMP[21147091]
GO:0006954	inflammatory response	biological process	IDA[21147091]

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0048010	vascular endothelial growth factor receptor signaling pathway	biological process	IEA
GO:0032570	response to progesterone	biological process	IEA
GO:0009617	response to bacterium	biological process	NAS[16034137]
GO:0035684	helper T cell extravasation	biological process	ISS
GO:0014823	response to activity	biological process	IEA
GO:0090026	positive regulation of monocyte chemotaxis	biological process	IEA
GO:0045202	synapse	cellular component	IEA
GO:0090280	positive regulation of calcium ion import	biological process	IDA[10925302]
GO:0035690	cellular response to drug	biological process	IEA
GO:0030593	neutrophil chemotaxis	biological process	IBA
GO:0002523	leukocyte migration involved in inflammatory response	biological process	IEA
GO:0030968	endoplasmic reticulum unfolded protein response	biological process	TAS
GO:0031663	lipopolysaccharide-mediated signaling pathway	biological process	IDA[21147091]
GO:0001938	positive regulation of endothelial cell proliferation	biological process	IEA
GO:0008009	chemokine activity	molecular function	IEA
GO:0060135	maternal process involved in female pregnancy	biological process	IEA
GO:0005615	extracellular space	cellular component	IEA
GO:0010759	positive regulation of macrophage chemotaxis	biological process	IEA
GO:0034351	negative regulation of glial cell apoptotic process	biological process	IDA[12753088]
GO:0031100	organ regeneration	biological process	IEA
GO:0019725	cellular homeostasis	biological process	TAS[18334747]
GO:0048471	perinuclear region of cytoplasm	cellular component	IEA
GO:0043547	positive regulation of GTPase activity	biological process	IBA
GO:0071403	cellular response to high density lipoprotein particle stimulus	biological process	IEA
GO:0032967	positive regulation of collagen biosynthetic process	biological process	IEA
GO:0033552	response to vitamin B3	biological process	IEA
GO:0007186	G-protein coupled receptor signaling pathway	biological process	TAS[10542238]
GO:0043615	astrocyte cell migration	biological process	IDA[12271471]
GO:0071407	cellular response to organic cyclic compound	biological process	IDA[21147091]
GO:0006959	humoral immune response	biological process	TAS[9548499]
GO:0030139	endocytic vesicle	cellular component	IEA
GO:0001666	response to hypoxia	biological process	IEA
GO:0031727	CCR2 chemokine receptor binding	molecular function	ISS; TAS[18021937]
GO:0005576	extracellular region	cellular component	IDA[20041150]; TAS
GO:0060137	maternal process involved in parturition	biological process	IEA
GO:0007155	cell adhesion	biological process	TAS[10198043]
GO:0007166	cell surface receptor signaling pathway	biological process	TAS[9548499]
GO:0009612	response to mechanical stimulus	biological process	IEA
GO:0071300	cellular response to retinoic acid	biological process	IEA
GO:2000502	negative regulation of natural killer cell chemotaxis	biological process	IDA[7545673]
GO:0036120	cellular response to platelet-derived growth factor stimulus	biological process	IEA
GO:0008201	heparin binding	molecular function	IEA
GO:0030425	dendrite	cellular component	IEA
GO:0008360	regulation of cell shape	biological process	IDA[10072545]
GO:0044344	cellular response to fibroblast growth factor stimulus	biological process	IEP[9407497]
GO:0007165	signal transduction	biological process	NAS[10770925]
GO:0004672	protein kinase activity	molecular function	TAS[9973507]
GO:0071549	cellular response to dexamethasone stimulus	biological process	IEA
GO:0071318	cellular response to ATP	biological process	IEA
GO:0019221	cytokine-mediated signaling pathway	biological process	IDA[12207323]
GO:0050729	positive regulation of inflammatory response	biological process	IBA
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process	biological process	ISS
GO:0036006	cellular response to macrophage colony-stimulating factor stimulus	biological process	IEA
GO:0002548	monocyte chemotaxis	biological process	IDA[12207323]
GO:0001525	angiogenesis	biological process	TAS[18334747]
GO:0070374	positive regulation of ERK1 and ERK2 cascade	biological process	IBA
GO:0006468	protein phosphorylation	biological process	TAS[9670957]
GO:0050870	positive regulation of T cell activation	biological process	ISS
GO:0007259	JAK-STAT cascade	biological process	TAS[9670957]
GO:0046677	response to antibiotic	biological process	IEA
GO:0071347	cellular response to interleukin-1	biological process	IEP[9407497]; ISS
GO:0001912	positive regulation of leukocyte mediated cytotoxicity	biological process	IEA
GO:2000427	positive regulation of apoptotic cell clearance	biological process	ISS
GO:0043524	negative regulation of neuron apoptotic process	biological process	IDA[12753088]
GO:0005102	receptor binding	molecular function	TAS[10542238]
GO:0010574	regulation of vascular endothelial growth factor production	biological process	IEA
GO:0043200	response to amino acid	biological process	IEA
GO:0009611	response to wounding	biological process	IEA
GO:0048246	macrophage chemotaxis	biological process	IDA[12207323]
GO:0044299	C-fiber	cellular component	IEA
GO:0071346	cellular response to interferon-gamma	biological process	IEP[9407497]; ISS
GO:0071356	cellular response to tumor necrosis factor	biological process	IEP[9407497]; ISS
GO:0016525	negative regulation of angiogenesis	biological process	IEA
GO:0007568	aging	biological process	IEA
GO:0070098	chemokine-mediated signaling pathway	biological process	IBA
GO:0045471	response to ethanol	biological process	IEA
GO:0090314	positive regulation of protein targeting to membrane	biological process	IEA
GO:0009408	response to heat	biological process	IEA
GO:0009887	organ morphogenesis	biological process	TAS[9364936]
GO:0048247	lymphocyte chemotaxis	biological process	IBA
GO:0036499	PERK-mediated unfolded protein response	biological process	TAS
GO:0006935	chemotaxis	biological process	TAS[10623817]
GO:0071354	cellular response to interleukin-6	biological process	IEA
GO:0043204	perikaryon	cellular component	IEA
GO:0044267	cellular protein metabolic process	biological process	TAS
GO:0032760	positive regulation of tumor necrosis factor production	biological process	IEA
GO:0005791	rough endoplasmic reticulum	cellular component	IEA
GO:0043679	axon terminus	cellular component	IEA
GO:0006874	cellular calcium ion homeostasis	biological process	IEA
GO:0002693	positive regulation of cellular extravasation	biological process	IEA
GO:0007179	transforming growth factor beta receptor signaling pathway	biological process	IEA
GO:0007010	cytoskeleton organization	biological process	IDA[10072545]
GO:0050806	positive regulation of synaptic transmission	biological process	IEA
GO:0007187	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	biological process	TAS[10770925]
GO:0019079	viral genome replication	biological process	TAS[10985244]
GO:0090265	positive regulation of immune complex clearance by monocytes and macrophages	biological process	IEA
GO:0071222	cellular response to lipopolysaccharide	biological process	ISS
GO:0010332	response to gamma radiation	biological process	IEA

CCL2 related KEGG pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04062	chemokine signaling_pathway	Chemokine signaling pathway	Inflammatory immune response requires the recruitment of leu...... Inflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for the cell trafficking and thus are vital for protective host response. In addition, chemokines regulate plethora of biological processes of hematopoietic cells to lead cellular activation, differentiation and survival. The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. Various members of small GTPases are involved in this process. Induction of nitric oxide and production of reactive oxygen species are as well regulated by chemokine signal via calcium mobilization and diacylglycerol production. More...
hsa04060	cytokine cytokine_receptor_interaction	Cytokine-cytokine receptor interaction	Cytokines are soluble extracellular proteins or glycoprotein...... Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped. More...
hsa04621	nod like_receptor_signaling_pathway	NOD-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. These NLRs include NALP1, NALP3 and Ipaf. The inflammasomes are critical for generating mature proinflammatory cytokines in concert with Toll-like receptor signaling pathway. More...

CCL2 related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
CCR5_PATHWAY	ccr5 pathway	Pertussis toxin-insensitive CCR5 Signaling in Macrophage	The chemokine receptors CCR5 and CXCR4 in macrophages are ac...... The chemokine receptors CCR5 and CXCR4 in macrophages are activated by their peptide ligands and also by the HIV envelope protein GP120 during HIV infection. One mechanism of signaling by these GPCRs is through activation of Gi signaling. These chemokine receptors can also signal through a Gi-independent pertussis toxin-insensitive pathway. This pathway elevates calcium influx into the cell through CRAC channels, ion channels that are activated by calcium release. Elevated calcium from CRAC is required for downstream activation of Pyk2, a focal adhesion-associated protein kinase. Non Gi signaling by these chemokine receptors also involves the Jnk and p38 Map kinase pathways leading to AP-1 activation and activation of genes such as MIP-1 and MCP-1. This pathway may be involved in the role of macrophages in the pathogenesis of AIDS. More...

CCL2 related Reactome pathways (count: 4)

ID	Name	Description
Gene mapped Reactome pathways
REACT_14819	peptide ligand_binding_receptors	These receptors, a subset of the Class A/1 (Rhodopsin-like) ...... These receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins. More...
REACT_14828	class a1_rhodopsin_like_receptors	Rhodopsin-like receptors. They represent members which inclu...... Rhodopsin-like receptors. They represent members which include hormone, light and neurotransmitter receptors and encompass a wide range of functions including many autocrine, paracrine and endocrine processes. More...
REACT_21340	gpcr ligand_binding	There are more than 800 G-protein coupled receptor. GPCRs ar...... There are more than 800 G-protein coupled receptor. GPCRs are receptors for a diverse range of ligands from large proteins to photons and have an equal diverstiy of ligand-binding mechanisms. Classical GPCR signaling involves signal transduction via heterotrimeric G-proteins, however many G-protein independent mechanisms have been reported. More...
REACT_15344	chemokine receptors_bind_chemokines	Chemokine receptors are cytokine receptors found on the surf...... Chemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of intracellular calcium which leads to chemotaxis. Chemokine receptors are divided into different families, CXC chemokine receptors, CC chemokine receptors, CX3C chemokine receptors and XC chemokine receptors that correspond to the 4 distinct subfamilies of chemokines they bind. More...

CCL2 related interactors from protein-protein interaction data in HPRD (count: 12)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
CCL2	VCAN	Yes	in vitro	11083865
CCL2	CCRL1	No	in vitro	10734104
CCL2	CCR2	No	in vitro;in vivo	10529171 , 9287323
CCL2	CCBP2	No	in vivo	9364936 , 9405404
CCL2	CCR1	No	in vitro	8631787
CCL2	MMP8	No	in vitro;in vivo	12149192 , 9558113
CCL2	MMP1	No	in vitro;in vivo	12149192 , 9558113
CCL2	DARC	No	in vitro;in vivo	13679391 , 17416748
CCL2	MMP3	No	in vitro;in vivo	12149192 , 9558113
CCL2	CCL2	Yes	in vitro	8639605 , 8989326 , 7651403
CCL2	CCR10	No	in vitro;in vivo	9364936 , 10706668
CCL2	CCR5	No	in vivo	10477718

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways