CCL2
C-C motif chemokine 2
Also known as: CCL2_HUMAN, GDCF-2, HC11, MCAF, MCP-1, MCP1, MGC9434, SCYA2, SMC-CF
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P13500
- Gene
- CCL2
- Ensembl
- ENSG00000108691
- Chromosome
- 17
- Canonical length
- 99 aa
- Protein class
- Cancer-related genes, Candidate cardiovascular disease genes, Human disease related genes, Plasma proteins, Predicted secreted proteins
- Subcellular location
- Golgi apparatus,Vesicles
- Secretome location
- Secreted to blood
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene is one of several cytokine genes clustered on the q-arm of chromosome 17. Chemokines are a superfamily of secreted proteins involved in immunoregulatory and inflammatory processes. The superfamily is divided into four subfamilies based on the arrangement of N-terminal cysteine residues of the mature peptide. This chemokine is a member of the CC subfamily which is characterized by two adjacent cysteine residues. This cytokine displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. [provided by RefSeq, Aug 2020]
Canonical amino-acid sequenceUniProt
99 residues, UniProt reviewed canonical sequence.
>P13500|CCL2
1 MKVSAALLCL LLIAATFIPQ GLAQPDAINA PVTCCYNFTN RKISVQRLAS YRRITSSKCP
61 KEAVIFKTIV AKEICADPKQ KWVQDSMDHL DKQTQTPKTLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CCL2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Secreted
- Secreted
- Yes
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.44
- Highest tissue expression
- 701 nTPM
Expression across tissuesHPA
Tissue
- urinary bladder: 701 nTPM
- lung: 409 nTPM
- adipose tissue: 375 nTPM
- heart muscle: 305 nTPM
- gallbladder: 235 nTPM
- blood vessel: 216 nTPM
Single-cell type
- pancreatic duct cells: 2,177 nCPM
- epididymal efferent duct ciliated cells: 1,814 nCPM
- epididymal efferent duct absorptive cells: 1,702 nCPM
- fallopian secretory cells: 1,596 nCPM
- pericytes: 1,395 nCPM
- vascular smooth muscle cells: 1,094 nCPM
Immune cell
- classical monocyte: 7.6 nTPM
- eosinophil: 3.1 nTPM
- total PBMC: 1.6 nTPM
- myeloid DC: 0.8 nTPM
- neutrophil: 0.6 nTPM
- intermediate monocyte: 0.2 nTPM
Brain region
- thalamus: 63 nTPM
- medulla oblongata: 37 nTPM
- cerebral cortex: 26 nTPM
- white matter: 26 nTPM
- choroid plexus: 25 nTPM
- hypothalamus: 21 nTPM
ReferencesPubMed · IEDB
Publications for CCL2 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
8 publications
- Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis.
2001 · J Exp Med · RCR 8.9 · 456 citations - Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines.
1998 · J Exp Med · RCR 1.9 · 100 citations - Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes.
1993 · J Immunol · RCR 1.8 · 77 citations - Restored immunosuppressive effect of mesenchymal stem cells on B cells after olfactory 1/early B cell factor-associated zinc-finger protein down-regulation in patients with systemic lupus erythematosus.
2014 · Arthritis Rheumatol · RCR 1.1 · 31 citations - Predominant expression of CCL2 at the tumor site of prostate cancer patients directs a selective loss of immunological tolerance to CCL2 that could be amplified in a beneficial manner.
2010 · J Immunol · RCR 0.8 · 38 citations
Show 3 more
- DNA vaccination with naked DNA encoding MCP-1 and RANTES protects against renal injury in adriamycin nephropathy.
2005 · Kidney Int · RCR 0.8 · 35 citations - DNA vaccination with CCL2 DNA modified by the addition of an adjuvant epitope protects against "nonimmune" toxic renal injury.
2006 · J Am Soc Nephrol · RCR 0.6 · 29 citations - CCL2 DNA vaccine to treat renal disease.
2009 · Int J Biochem Cell Biol · RCR 0.2 · 8 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1
- gnomAD pLI
- 0.61
- gnomAD missense Z
- 1.19
- DepMap mean gene effect
- 0.09
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- angiogenesis
- animal organ morphogenesis
- antimicrobial humoral immune response mediated by antimicrobial peptide
- astrocyte cell migration
- cell adhesion
- cell surface receptor signaling pathway
- cell surface receptor signaling pathway via JAK-STAT
- cellular homeostasis
- cellular response to fibroblast growth factor stimulus
- cellular response to interleukin-1
- cellular response to lipopolysaccharide
- cellular response to tumor necrosis factor
- cellular response to type II interferon
- chemokine-mediated signaling pathway
- chemotaxis
- cytokine-mediated signaling pathway
- cytoskeleton organization
- eosinophil chemotaxis
- G protein-coupled receptor signaling pathway
- G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
- humoral immune response
- inflammatory response
- macrophage chemotaxis
- monocyte chemotaxis
- negative regulation of G1/S transition of mitotic cell cycle
- negative regulation of glial cell apoptotic process
- negative regulation of natural killer cell chemotaxis
- negative regulation of neuron apoptotic process
- negative regulation of vascular endothelial cell proliferation
- positive regulation of apoptotic cell clearance
- positive regulation of calcium ion import
- positive regulation of cell migration
- positive regulation of cytosolic calcium ion concentration
- positive regulation of endothelial cell apoptotic process
- positive regulation of gene expression
- positive regulation of glutamate receptor signaling pathway
- positive regulation of macrophage chemotaxis
- positive regulation of synaptic transmission, glutamatergic
- positive regulation of T cell activation
- protein phosphorylation
- regulation of cell shape
- response to bacterium
- sensory perception of pain
- signal transduction
- viral genome replication
- chemokine (C-C motif) ligand 2 signaling pathway
- helper T cell extravasation
Molecular functions
- CCR chemokine receptor binding
- CCR2 chemokine receptor binding
- chemoattractant activity
- chemokine activity
- chemokine receptor binding
- protein kinase activity
- signaling receptor binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CCL2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CCL2 as an antibody target. Whether an autoantibody or antibody against CCL2 could matter depends on whether native CCL2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CCL2 is annotated as secreted, so native CCL2 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.
Annotation status
The present source text does not explicitly label CCL2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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