Target type: molecularfunction
Binding to chemokine (C-C motif) ligand 12. [GOC:BHF]
Chemokine (C-C motif) ligand 12 (CCL12), also known as monocyte chemoattractant protein-5 (MCP-5), is a small cytokine belonging to the CC chemokine family. It plays a crucial role in immune cell trafficking and inflammation by binding to its primary receptor, CCR2. CCL12's molecular function involves the following steps:
1. **Binding to CCR2:** CCL12 specifically interacts with the extracellular domain of CCR2, a G protein-coupled receptor (GPCR) expressed on the surface of various immune cells, including monocytes, macrophages, and dendritic cells. This binding event triggers a conformational change in CCR2.
2. **Activation of G protein signaling:** The conformational change in CCR2 leads to the activation of a heterotrimeric G protein associated with the receptor. This activation involves the dissociation of the Gα subunit from the Gβγ dimer.
3. **Signal transduction cascade:** The activated Gα subunit, typically Gαi, interacts with downstream signaling molecules, such as phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K). This interaction initiates intracellular signaling cascades.
4. **Chemotaxis:** The activated signaling pathways ultimately lead to the polymerization of actin filaments and the reorganization of the cell's cytoskeleton. This results in directed cell migration towards the source of CCL12, a process known as chemotaxis.
5. **Cell activation:** CCL12 binding to CCR2 can also activate other intracellular signaling pathways, leading to the production of inflammatory mediators, such as cytokines and chemokines, further amplifying the inflammatory response.
6. **Immune cell recruitment:** CCL12 plays a key role in attracting monocytes and macrophages to sites of inflammation, where they contribute to the clearance of pathogens and tissue repair.
In summary, CCL12's molecular function involves binding to its receptor CCR2, activating intracellular signaling cascades, and promoting chemotaxis and immune cell recruitment. This complex interplay of molecular events underpins CCL12's essential role in regulating immune responses and inflammation.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| C-C chemokine receptor type 2 | A C-C chemokine receptor type 2 that is encoded in the genome of human. [PRO:WCB, UniProtKB:P41597] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| amiodarone | amiodarone : A member of the class of 1-benzofurans that is 1-benzofuran substituted by a butyl group at position 2 and a 4-[2-(diethylamino)ethoxy]-3,5-diiodobenzoyl group at position 3. It is a cardiovascular drug used for the treatment of cardiac dysrhythmias. Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance. | 1-benzofurans; aromatic ketone; organoiodine compound; tertiary amino compound | cardiovascular drug |
| disulfiram | organic disulfide; organosulfur acaricide | angiogenesis inhibitor; antineoplastic agent; apoptosis inducer; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 3.1.1.1 (carboxylesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; ferroptosis inducer; fungicide; NF-kappaB inhibitor | |
| fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
| nifedipine | Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. | C-nitro compound; dihydropyridine; methyl ester | calcium channel blocker; human metabolite; tocolytic agent; vasodilator agent |
| dibenzothiazyl disulfide | dibenzothiazol-2-yl disulfide : An organic disulfide resulting from the formal oxidative coupling of the thiol groups of two molecules of 1,3-benzothiazole-2-thiol. It is used as an accelerator in the rubber industry. dibenzothiazyl disulfide: vulcanizing accelerant | benzothiazoles; organic disulfide | allergen |
| 1-naphthylisothiocyanate | 1-Naphthylisothiocyanate: A tool for the study of liver damage which causes bile stasis and hyperbilirubinemia acutely and bile duct hyperplasia and biliary cirrhosis chronically, with changes in hepatocyte function. It may cause skin and kidney damage. | isothiocyanate | insecticide |
| plerixafor | plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2 | azacycloalkane; azamacrocycle; benzenes; crown amine; secondary amino compound; tertiary amino compound | anti-HIV agent; antineoplastic agent; C-X-C chemokine receptor type 4 antagonist; immunological adjuvant |
| rosiglitazone | aminopyridine; thiazolidinediones | EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor; ferroptosis inhibitor; insulin-sensitizing drug | |
| fasudil hydrochloride | fasudil hydrochloride : A hydrochloride obtained by reaction of fasudil with one equivalent of hydrochloric acid. | hydrochloride | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; neuroprotective agent; nootropic agent; vasodilator agent |
| tak 779 | |||
| bay 11-7085 | BAY11-7085 : A sulfone that is benzene substituted by [(E)-2-cyanoethenyl]sulfonyl and tert-butyl groups at position 1 and 4, respectively. It is an irreversible inhibitor of IkappaB-alpha phosphorylation in cells (IC50 = 10 muM) and prevents the activation of NF-kappaB. | benzenes; nitrile; sulfone | anti-inflammatory agent; antibacterial agent; antineoplastic agent; apoptosis inducer; autophagy inducer; EC 2.7.11.10 (IkappaB kinase) inhibitor; ferroptosis inducer; NF-kappaB inhibitor |
| ucb 35625 | UCB 35625: J-113863 is the (trans)-isomer; structure in first source | ||
| rs 504393 | RS 504393: structure in first source | 1,3-oxazoles | |
| incb3344 | INCB3344: potent and selective small molecule CCR2 chemokine receptor antagonist | ||
| amd 070 | mavorixafor: a derivative of AMD3100; a CXCR4 blocker | aminoquinoline | |
| cenicriviroc | cenicriviroc : A member of the class of benzazocines that is (5Z)-1,2,3,4-tetrahydro-1-benzazocine which is substituted by a 2-methylpropyl, N-{4-[(S)-(1-propyl-1H-imidazol-5-yl)methanesulfinyl]phenyl}carboxamide and 4-(2-butoxyethoxy)phenyl groups at positions 1, 5 and 8, respectively. It is a potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). cenicriviroc: an inhibitor of HIV-1 | aromatic ether; benzazocine; diether; imidazoles; secondary carboxamide; sulfoxide | anti-HIV agent; anti-inflammatory agent; antirheumatic drug; chemokine receptor 2 antagonist; chemokine receptor 5 antagonist |
| incb 3284 | INCB 3284: a CCR2 receptor antagonist | ||
| azd8309 | AZD8309: CXCR2 inhibitor | ||
| n-(carbamoylmethyl)-3-trifluoromethyl benzamido-4-chlorobenzyl 3-aminopyrrolidine |