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Protein

C-C motif chemokine 2

Gene

CCL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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: ProtInc
  • protein kinase activity Source: ProtInc
  • 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 glial cell apoptotic process Source: UniProtKB
  • negative regulation of natural killer cell chemotaxis Source: UniProtKB
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • 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 ERK1 and ERK2 cascade Source: GO_Central
  • positive regulation of GTPase activity Source: GO_Central
  • positive regulation of inflammatory response 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
Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108691-MONOMER.
ReactomeiR-HSA-380994. ATF4 activates genes.
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

HGNCiHGNC:10618. CCL2.

Subcellular locationi

GO - Cellular componenti

  • extracellular region Source: BHF-UCL
  • extracellular space Source: ProtInc
Complete GO annotation...

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...)Sequence 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.

Miscellaneous databases

PMAP-CutDBP13500.

Expressioni

Tissue specificityi

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

Inductioni

Up-regulated upon hypertonic conditions.1 Publication

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

WithEntry#Exp.IntActNotes
TNFAIP6P980662EBI-11711396,EBI-11700693

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112251. 14 interactors.
DIPiDIP-5838N.
IntActiP13500. 2 interactors.
MINTiMINT-103269.
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

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DOKX-ray1.85A/B24-99[»]
1DOLX-ray2.40A24-99[»]
1DOMNMR-A/B24-99[»]
1DONNMR-A/B24-99[»]
1MCAmodel-A/B24-96[»]
1ML0X-ray2.80D24-99[»]
2BDNX-ray2.53A24-99[»]
2NZ1X-ray2.50D/E/Y24-99[»]
3IFDX-ray1.90A24-99[»]
4DN4X-ray2.80M24-99[»]
4R8IX-ray2.05A24-99[»]
4ZK9X-ray2.60B24-99[»]
ProteinModelPortaliP13500.
SMRiP13500.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13500.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1ST. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036686.
HOVERGENiHBG017871.
InParanoidiP13500.
KOiK14624.
OMAiNKEICAD.
OrthoDBiEOG091G14KV.
PhylomeDBiP13500.
TreeFamiTF334888.

Family and domain databases

InterProiIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]

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.

Cross-referencesi

Web resourcesi

Wikipedia

CCL2 entry

SeattleSNPs

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1DOKX-ray1.85A/B24-99[»]
1DOLX-ray2.40A24-99[»]
1DOMNMR-A/B24-99[»]
1DONNMR-A/B24-99[»]
1MCAmodel-A/B24-96[»]
1ML0X-ray2.80D24-99[»]
2BDNX-ray2.53A24-99[»]
2NZ1X-ray2.50D/E/Y24-99[»]
3IFDX-ray1.90A24-99[»]
4DN4X-ray2.80M24-99[»]
4R8IX-ray2.05A24-99[»]
4ZK9X-ray2.60B24-99[»]
ProteinModelPortaliP13500.
SMRiP13500.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112251. 14 interactors.
DIPiDIP-5838N.
IntActiP13500. 2 interactors.
MINTiMINT-103269.
STRINGi9606.ENSP00000225831.

Chemistry databases

BindingDBiP13500.
ChEMBLiCHEMBL1649052.
DrugBankiDB01406. Danazol.
DB01055. Mimosine.

Polymorphism and mutation databases

BioMutaiCCL2.
DMDMi126842.

Proteomic databases

PaxDbiP13500.
PeptideAtlasiP13500.
PRIDEiP13500.

Protocols and materials databases

DNASUi6347.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi6347.
DisGeNETi6347.
GeneCardsiCCL2.
HGNCiHGNC:10618. CCL2.
HPAiCAB013676.
HPA019163.
MalaCardsiCCL2.
MIMi158105. gene.
607948. phenotype.
neXtProtiNX_P13500.
OpenTargetsiENSG00000108691.
PharmGKBiPA130413151.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J1ST. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00860000133690.
HOGENOMiHOG000036686.
HOVERGENiHBG017871.
InParanoidiP13500.
KOiK14624.
OMAiNKEICAD.
OrthoDBiEOG091G14KV.
PhylomeDBiP13500.
TreeFamiTF334888.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000108691-MONOMER.
ReactomeiR-HSA-380994. ATF4 activates genes.
SIGNORiP13500.

Miscellaneous databases

EvolutionaryTraceiP13500.
GeneWikiiCCL2.
GenomeRNAii6347.
PMAP-CutDBP13500.
PROiP13500.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000108691.
CleanExiHS_CCL2.
ExpressionAtlasiP13500. baseline and differential.
GenevisibleiP13500. HS.

Family and domain databases

InterProiIPR000827. Chemokine_CC_CS.
IPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMiSSF54117. SSF54117. 1 hit.
PROSITEiPS00472. SMALL_CYTOKINES_CC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCL2_HUMAN
AccessioniPrimary (citable) accession number: P13500
Secondary accession number(s): B2R4V3, Q9UDF3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1990
Last sequence update: January 1, 1990
Last modified: November 30, 2016
This is version 204 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.