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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)LengthDescriptionGraphical viewFeature identifierActions
Sitei31 – 311Involved in dimerization
Sitei36 – 361Involved in dimerization, receptor binding and signaling
Sitei41 – 411Involved in GAG binding
Sitei42 – 421Involved in GAG binding
Sitei47 – 471Involved in GAG binding and receptor binding
Sitei58 – 581Involved in dimerization
Sitei61 – 611Involved in dimerization
Sitei72 – 721Involved in GAG binding and receptor binding
Sitei81 – 811Involved in GAG binding
Sitei89 – 891Involved in GAG binding

GO - Molecular functioni

  • CCR2 chemokine receptor binding Source: BHF-UCL
  • chemokine activity Source: ProtInc
  • heparin binding Source: Ensembl
  • protein kinase activity Source: ProtInc
  • receptor binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Cytokine

Keywords - Biological processi

Chemotaxis, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-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

  • axon terminus Source: Ensembl
  • C-fiber Source: Ensembl
  • dendrite Source: Ensembl
  • endocytic vesicle Source: Ensembl
  • extracellular region Source: BHF-UCL
  • extracellular space Source: ProtInc
  • perikaryon Source: Ensembl
  • perinuclear region of cytoplasm Source: Ensembl
  • rough endoplasmic reticulum Source: Ensembl
  • synapse Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi24 – 9168Missing : 83% reduction in activity. Add
BLAST
Mutagenesisi24 – 8562Missing : 90% reduction in activity. Add
BLAST
Mutagenesisi24 – 241Missing : Loss of activity.
Mutagenesisi25 – 317Missing : Loss of signaling. 1 Publication
Mutagenesisi26 – 261D → A: Reduction in activity. 1 Publication
Mutagenesisi28 – 281I → A: Slight reduction in activity. 1 Publication
Mutagenesisi29 – 291N → A: 50% reduction in activity. 1 Publication
Mutagenesisi31 – 311P → A: Loss of dimerization; slight reduction of activity. 2 Publications
Mutagenesisi32 – 321V → A: Slight reduction in activity. 2 Publications
Mutagenesisi32 – 321V → E: Slight reduction in affinity. 2 Publications
Mutagenesisi33 – 331T → A: Slight reduction in activity. 2 Publications
Mutagenesisi33 – 331T → E: Slight reduction in affinity. 2 Publications
Mutagenesisi36 – 361Y → A: Loss of activity. 1 Publication
Mutagenesisi47 – 471R → F: 95% reduction in activity; strong reduction of receptor binding.
Mutagenesisi50 – 501S → Q: 40% reduction in activity.
Mutagenesisi51 – 511Y → D: Loss of activity.
Mutagenesisi53 – 531R → L: Loss of activity.
Mutagenesisi79 – 791K → A: No effect on heparin binding.
Mutagenesisi81 – 811K → A: Strongly reduces heparin binding. 1 Publication
Mutagenesisi89 – 891H → A: Strongly reduces heparin binding. 1 Publication
Mutagenesisi91 – 911D → L: 90% reduction in activity.
Mutagenesisi95 – 995Missing : No effect on heparin binding. 1 Publication

Organism-specific databases

MalaCardsiCCL2.
MIMi607948. phenotype.
PharmGKBiPA130413151.

Chemistry

ChEMBLiCHEMBL1649052.
DrugBankiDB01406. Danazol.
DB01055. Mimosine.

Polymorphism and mutation databases

BioMutaiCCL2.
DMDMi126842.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 9976C-C motif chemokine 2PRO_0000005146Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei24 – 241Pyrrolidone carboxylic acid2 Publications
Disulfide bondi34 ↔ 59
Disulfide bondi35 ↔ 75
Glycosylationi37 – 371N-linked (GlcNAc...)Sequence analysis

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

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112251. 14 interactions.
DIPiDIP-5838N.
IntActiP13500. 1 interaction.
MINTiMINT-103269.
STRINGi9606.ENSP00000225831.

Chemistry

BindingDBiP13500.

Structurei

Secondary structure

1
99
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi25 – 295Combined sources
Beta strandi32 – 343Combined sources
Helixi45 – 473Combined sources
Beta strandi48 – 547Combined sources
Beta strandi59 – 613Combined sources
Beta strandi63 – 686Combined sources
Beta strandi73 – 764Combined sources
Beta strandi78 – 803Combined sources
Helixi81 – 9212Combined sources
Beta strandi93 – 953Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 24-94.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP13500.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1ST. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00730000110714.
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
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. Positions 24-94.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112251. 14 interactions.
DIPiDIP-5838N.
IntActiP13500. 1 interaction.
MINTiMINT-103269.
STRINGi9606.ENSP00000225831.

Chemistry

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

Phylogenomic databases

eggNOGiENOG410J1ST. Eukaryota.
ENOG410YXJU. LUCA.
GeneTreeiENSGT00730000110714.
HOGENOMiHOG000036686.
HOVERGENiHBG017871.
InParanoidiP13500.
KOiK14624.
OMAiNKEICAD.
OrthoDBiEOG091G14KV.
PhylomeDBiP13500.
TreeFamiTF334888.

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.
R-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: September 7, 2016
This is version 201 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.