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Protein

C-C motif chemokine 2

Gene

CCL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Chemotactic factor that attracts monocytes and basophils but not neutrophils or eosinophils. Augments monocyte anti-tumor activity. Has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, like psoriasis, rheumatoid arthritis or atherosclerosis. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei31Involved in dimerization1
Sitei36Involved in dimerization, receptor binding and signaling1
Sitei41Involved in GAG binding1
Sitei42Involved in GAG binding1
Sitei47Involved in GAG binding and receptor binding1
Sitei58Involved in dimerization1
Sitei61Involved in dimerization1
Sitei72Involved in GAG binding and receptor binding1
Sitei81Involved in GAG binding1
Sitei89Involved in GAG binding1

GO - Molecular functioni

  • CCR2 chemokine receptor binding Source: BHF-UCL
  • chemokine activity Source: GO_Central
  • protein kinase activity Source: ProtInc
  • signaling receptor binding Source: ProtInc

GO - Biological processi

  • angiogenesis Source: BHF-UCL
  • animal organ morphogenesis Source: ProtInc
  • astrocyte cell migration Source: BHF-UCL
  • cell adhesion Source: ProtInc
  • cell surface receptor signaling pathway Source: ProtInc
  • cellular homeostasis Source: BHF-UCL
  • cellular response to fibroblast growth factor stimulus Source: UniProtKB
  • cellular response to interferon-gamma Source: UniProtKB
  • cellular response to interleukin-1 Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • cellular response to organic cyclic compound Source: UniProtKB
  • cellular response to tumor necrosis factor Source: UniProtKB
  • chemokine-mediated signaling pathway Source: GO_Central
  • chemotaxis Source: ProtInc
  • cytokine-mediated signaling pathway Source: BHF-UCL
  • cytoskeleton organization Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  • helper T cell extravasation Source: BHF-UCL
  • humoral immune response Source: ProtInc
  • inflammatory response Source: UniProtKB
  • JAK-STAT cascade Source: ProtInc
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • macrophage chemotaxis Source: BHF-UCL
  • MAPK cascade Source: UniProtKB
  • monocyte chemotaxis Source: BHF-UCL
  • negative regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
  • negative regulation of glial cell apoptotic process Source: UniProtKB
  • negative regulation of natural killer cell chemotaxis Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of vascular endothelial cell proliferation Source: BHF-UCL
  • neutrophil chemotaxis Source: GO_Central
  • PERK-mediated unfolded protein response Source: Reactome
  • positive regulation of apoptotic cell clearance Source: BHF-UCL
  • positive regulation of calcium ion import Source: BHF-UCL
  • positive regulation of endothelial cell apoptotic process Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: GO_Central
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  • positive regulation of T cell activation Source: BHF-UCL
  • protein kinase B signaling Source: UniProtKB
  • protein phosphorylation Source: ProtInc
  • regulation of cell shape Source: UniProtKB
  • response to bacterium Source: BHF-UCL
  • signal transduction Source: ProtInc
  • viral genome replication Source: ProtInc

Keywordsi

Molecular functionCytokine
Biological processChemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-380994 ATF4 activates genes
R-HSA-6783783 Interleukin-10 signaling
R-HSA-6785807 Interleukin-4 and 13 signaling
SIGNORiP13500

Names & Taxonomyi

Protein namesi
Recommended name:
C-C motif chemokine 2
Alternative name(s):
HC11
Monocyte chemoattractant protein 1
Monocyte chemotactic and activating factor
Short name:
MCAF
Monocyte chemotactic protein 1
Short name:
MCP-1
Monocyte secretory protein JE
Small-inducible cytokine A2
Gene namesi
Name:CCL2
Synonyms:MCP1, SCYA2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000108691.9
HGNCiHGNC:10618 CCL2
MIMi158105 gene
neXtProtiNX_P13500

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24 – 91Missing : 83% reduction in activity. Add BLAST68
Mutagenesisi24 – 85Missing : 90% reduction in activity. Add BLAST62
Mutagenesisi24Missing : Loss of activity. 1
Mutagenesisi25 – 31Missing : Loss of signaling. 1 Publication7
Mutagenesisi26D → A: Reduction in activity. 1 Publication1
Mutagenesisi28I → A: Slight reduction in activity. 1 Publication1
Mutagenesisi29N → A: 50% reduction in activity. 1 Publication1
Mutagenesisi31P → A: Loss of dimerization; slight reduction of activity. 2 Publications1
Mutagenesisi32V → A: Slight reduction in activity. 2 Publications1
Mutagenesisi32V → E: Slight reduction in affinity. 2 Publications1
Mutagenesisi33T → A: Slight reduction in activity. 2 Publications1
Mutagenesisi33T → E: Slight reduction in affinity. 2 Publications1
Mutagenesisi36Y → A: Loss of activity. 1 Publication1
Mutagenesisi47R → F: 95% reduction in activity; strong reduction of receptor binding. 1
Mutagenesisi50S → Q: 40% reduction in activity. 1
Mutagenesisi51Y → D: Loss of activity. 1
Mutagenesisi53R → L: Loss of activity. 1
Mutagenesisi79K → A: No effect on heparin binding. 1
Mutagenesisi81K → A: Strongly reduces heparin binding. 1 Publication1
Mutagenesisi89H → A: Strongly reduces heparin binding. 1 Publication1
Mutagenesisi91D → L: 90% reduction in activity. 1
Mutagenesisi95 – 99Missing : No effect on heparin binding. 1 Publication5

Organism-specific databases

DisGeNETi6347
MalaCardsiCCL2
MIMi607948 phenotype
OpenTargetsiENSG00000108691
PharmGKBiPA130413151

Chemistry databases

ChEMBLiCHEMBL1649052
DrugBankiDB01406 Danazol
DB01055 Mimosine

Polymorphism and mutation databases

BioMutaiCCL2
DMDMi126842

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000000514624 – 99C-C motif chemokine 2Add BLAST76

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei24Pyrrolidone carboxylic acid2 Publications1
Disulfide bondi34 ↔ 59
Disulfide bondi35 ↔ 75
Glycosylationi37N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Processing at the N-terminus can regulate receptor and target cell selectivity. Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant.

Keywords - PTMi

Disulfide bond, Glycoprotein, Pyrrolidone carboxylic acid

Proteomic databases

PaxDbiP13500
PeptideAtlasiP13500
PRIDEiP13500
ProteomicsDBi52921

Miscellaneous databases

PMAP-CutDBiP13500

Expressioni

Tissue specificityi

Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level).1 Publication

Inductioni

Up-regulated upon hypertonic conditions (PubMed:23233732). In pancreatic islets, secretion is stimulated by IL1B (PubMed:23955712).2 Publications

Gene expression databases

BgeeiENSG00000108691
CleanExiHS_CCL2
ExpressionAtlasiP13500 baseline and differential
GenevisibleiP13500 HS

Organism-specific databases

HPAiCAB013676
HPA019163

Interactioni

Subunit structurei

Monomer or homodimer; in equilibrium. Binds to CCR2 and CCR4. Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • CCR2 chemokine receptor binding Source: BHF-UCL
  • chemokine activity Source: GO_Central
  • signaling receptor binding Source: ProtInc

Protein-protein interaction databases

BioGridi112251, 14 interactors
DIPiDIP-5838N
IntActiP13500, 6 interactors
STRINGi9606.ENSP00000225831

Chemistry databases

BindingDBiP13500

Structurei

Secondary structure

199
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi25 – 29Combined sources5
Beta strandi32 – 34Combined sources3
Helixi45 – 47Combined sources3
Beta strandi48 – 54Combined sources7
Beta strandi59 – 61Combined sources3
Beta strandi63 – 68Combined sources6
Beta strandi73 – 76Combined sources4
Beta strandi78 – 80Combined sources3
Helixi81 – 92Combined sources12
Beta strandi93 – 95Combined sources3

3D structure databases

ProteinModelPortaliP13500
SMRiP13500
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13500

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1ST Eukaryota
ENOG410YXJU LUCA
GeneTreeiENSGT00900000140949
HOGENOMiHOG000036686
HOVERGENiHBG017871
InParanoidiP13500
KOiK14624
OMAiKISMQRL
OrthoDBiEOG091G14KV
PhylomeDBiP13500
TreeFamiTF334888

Family and domain databases

InterProiView protein in InterPro
IPR000827 Chemokine_CC_CS
IPR001811 Chemokine_IL8-like_dom
IPR036048 Interleukin_8-like_sf
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit
PROSITEiView protein in PROSITE
PS00472 SMALL_CYTOKINES_CC, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P13500-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKVSAALLCL LLIAATFIPQ GLAQPDAINA PVTCCYNFTN RKISVQRLAS
60 70 80 90
YRRITSSKCP KEAVIFKTIV AKEICADPKQ KWVQDSMDHL DKQTQTPKT
Length:99
Mass (Da):11,025
Last modified:January 1, 1990 - v1
Checksum:i45EC72361435302F
GO

Polymorphismi

Genetic variations in CCL2 determine Mycobacterium tuberculosis susceptibility [MIMi:607948].1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M24545 mRNA Translation: AAA18164.1
M28225, M28223, M28224 Genomic DNA Translation: AAA60308.1
M28226 mRNA Translation: AAA60309.1
M31626, M30816, M31625 Genomic DNA Translation: AAA36330.1
X14768 mRNA Translation: CAA32876.1
M37719 Genomic DNA Translation: AAA18102.1
S71513 mRNA Translation: AAB20651.1
S69738 mRNA Translation: AAB29926.1
Y18933 Genomic DNA Translation: CAC14049.1
A17786 mRNA Translation: CAA01352.1
BT007329 mRNA Translation: AAP35993.1
AF519531 Genomic DNA Translation: AAM54046.1
AK311960 mRNA Translation: BAG34900.1
CH471147 Genomic DNA Translation: EAW80212.1
BC009716 mRNA Translation: AAH09716.1
CCDSiCCDS11277.1
PIRiA35474 A60299
RefSeqiNP_002973.1, NM_002982.3
UniGeneiHs.303649

Genome annotation databases

EnsembliENST00000225831; ENSP00000225831; ENSG00000108691
GeneIDi6347
KEGGihsa:6347
UCSCiuc002hhy.4 human

Similar proteinsi

Entry informationi

Entry nameiCCL2_HUMAN
AccessioniPrimary (citable) accession number: P13500
Secondary accession number(s): B2R4V3, Q9UDF3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: July 18, 2018
This is version 219 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

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