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Protein

C-C chemokine receptor type 2

Gene

CCR2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for the CCL2, CCL7 and CCL13 chemokines (PubMed:23408426). Receptor for the beta-defensin DEFB106A/DEFB106B (PubMed:23938203). Transduces a signal by increasing intracellular calcium ion levels (By similarity). Upon CCL2 ligation, mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion (Probable).By similarity1 Publication2 Publications
(Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.1 Publication

GO - Molecular functioni

  • C-C chemokine receptor activity Source: InterPro
  • CCR2 chemokine receptor binding Source: MGI
  • chemokine receptor activity Source: ProtInc
  • protein homodimerization activity Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processHost-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-1461957. Beta defensins.
R-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.
R-HSA-6783783. Interleukin-10 signaling.
SIGNORiP41597.

Names & Taxonomyi

Protein namesi
Recommended name:
C-C chemokine receptor type 2
Short name:
C-C CKR-2
Short name:
CC-CKR-2
Short name:
CCR-2
Short name:
CCR2
Alternative name(s):
Monocyte chemoattractant protein 1 receptor
Short name:
MCP-1-R
CD_antigen: CD192
Gene namesi
Name:CCR2
Synonyms:CMKBR2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000121807.5.
HGNCiHGNC:1603. CCR2.

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 42ExtracellularSequence analysisAdd BLAST42
Transmembranei43 – 70Helical; Name=1Sequence analysisAdd BLAST28
Topological domaini71 – 80CytoplasmicSequence analysis10
Transmembranei81 – 100Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini101 – 114ExtracellularSequence analysisAdd BLAST14
Transmembranei115 – 136Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini137 – 153CytoplasmicSequence analysisAdd BLAST17
Transmembranei154 – 178Helical; Name=4Sequence analysisAdd BLAST25
Topological domaini179 – 206ExtracellularSequence analysisAdd BLAST28
Transmembranei207 – 226Helical; Name=5Sequence analysisAdd BLAST20
Topological domaini227 – 243CytoplasmicSequence analysisAdd BLAST17
Transmembranei244 – 268Helical; Name=6Sequence analysisAdd BLAST25
Topological domaini269 – 285ExtracellularSequence analysisAdd BLAST17
Transmembranei286 – 309Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini310 – 374CytoplasmicSequence analysisAdd BLAST65

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi729230.
MIMi609423. phenotype.
OpenTargetsiENSG00000121807.
PharmGKBiPA26167.

Chemistry databases

ChEMBLiCHEMBL4015.
DrugBankiDB05159. CCX915.
DB05130. INCB3284.
DB05486. MLN-1202.
GuidetoPHARMACOLOGYi59.

Polymorphism and mutation databases

BioMutaiCCR2.
DMDMi1168965.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692321 – 374C-C chemokine receptor type 2Add BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi14N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei26Sulfotyrosine1 Publication1
Disulfide bondi113 ↔ 1901 Publication
Modified residuei139Phosphotyrosine; by JAK21 Publication1

Post-translational modificationi

N-glycosylated.1 Publication
Sulfation increases the affinity for both monomeric and dimeric CCL2 with stronger binding to the monomeric form. Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer to monomer.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Sulfation

Proteomic databases

PaxDbiP41597.
PeptideAtlasiP41597.
PRIDEiP41597.

PTM databases

iPTMnetiP41597.
PhosphoSitePlusiP41597.

Expressioni

Tissue specificityi

Expressed by monocytes and IL2-activated NK cells.1 Publication

Inductioni

Up-regulated by CREB3 (PubMed:18587271). In NK cells, induced by IL2 (PubMed:9058802).2 Publications

Gene expression databases

BgeeiENSG00000121807.
CleanExiHS_CCR2.
ExpressionAtlasiP41597. baseline and differential.
GenevisibleiP41597. HS.

Organism-specific databases

HPAiCAB003793.

Interactioni

Subunit structurei

Interacts with ARRB1 (PubMed:9501202). Interacts (via extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; this interaction may preferentially require specific tyrosine sulfation on CCR2 (PubMed:23938203). Interacts with NUP85; the interaction is required for CCR2 clusters formation on the cell membrane and CCR2 signaling (PubMed:15995708, PubMed:25283965).4 Publications
(Microbial infection) Binds to HIV-1 Tat.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
NUP85Q9BW273EBI-14807859,EBI-716392

GO - Molecular functioni

  • CCR2 chemokine receptor binding Source: MGI
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi609634. 1 interactor.
DIPiDIP-5833N.
IntActiP41597. 1 interactor.
MINTiMINT-5005983.
STRINGi9606.ENSP00000292301.

Chemistry databases

BindingDBiP41597.

Structurei

Secondary structure

1374
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi38 – 69Combined sources32
Helixi76 – 92Combined sources17
Helixi95 – 103Combined sources9
Helixi110 – 142Combined sources33
Helixi146 – 151Combined sources6
Helixi154 – 170Combined sources17
Helixi173 – 177Combined sources5
Beta strandi179 – 184Combined sources6
Beta strandi187 – 192Combined sources6
Helixi196 – 210Combined sources15
Helixi212 – 228Combined sources17
Helixi237 – 265Combined sources29
Turni266 – 268Combined sources3
Helixi269 – 272Combined sources4
Helixi279 – 295Combined sources17
Turni296 – 300Combined sources5
Helixi301 – 308Combined sources8
Helixi310 – 318Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KADmodel-A1-343[»]
1KP1model-A1-343[»]
2MLONMR-A310-318[»]
2MLQNMR-A310-318[»]
5T1AX-ray2.81A2-313[»]
ProteinModelPortaliP41597.
SMRiP41597.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP41597.
KOiK04177.
OMAiCPVFYRE.
OrthoDBiEOG091G0B7A.
PhylomeDBiP41597.
TreeFamiTF330966.

Family and domain databases

InterProiView protein in InterPro
IPR002237. Chemokine_CCR2.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PRINTSiPR00657. CCCHEMOKINER.
PR01107. CHEMOKINER2.
PR00237. GPCRRHODOPSN.
SMARTiView protein in SMART
SM01381. 7TM_GPCR_Srsx. 1 hit.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform A1 Publication (identifier: P41597-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLSTSRSRFI RNTNESGEEV TTFFDYDYGA PCHKFDVKQI GAQLLPPLYS
60 70 80 90 100
LVFIFGFVGN MLVVLILINC KKLKCLTDIY LLNLAISDLL FLITLPLWAH
110 120 130 140 150
SAANEWVFGN AMCKLFTGLY HIGYFGGIFF IILLTIDRYL AIVHAVFALK
160 170 180 190 200
ARTVTFGVVT SVITWLVAVF ASVPGIIFTK CQKEDSVYVC GPYFPRGWNN
210 220 230 240 250
FHTIMRNILG LVLPLLIMVI CYSGILKTLL RCRNEKKRHR AVRVIFTIMI
260 270 280 290 300
VYFLFWTPYN IVILLNTFQE FFGLSNCEST SQLDQATQVT ETLGMTHCCI
310 320 330 340 350
NPIIYAFVGE KFRSLFHIAL GCRIAPLQKP VCGGPGVRPG KNVKVTTQGL
360 370
LDGRGKGKSI GRAPEASLQD KEGA
Length:374
Mass (Da):41,915
Last modified:November 1, 1995 - v1
Checksum:iF865E0D39E74CF0F
GO
Isoform B1 Publication (identifier: P41597-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     314-374: SLFHIALGCR...EASLQDKEGA → RYLSVFFRKH...TGEQEVSAGL

Note: Mutagenesis of Leu-316 to Thr as well as Phe-320 to Asp decrease interaction with NUP85.1 Publication
Show »
Length:360
Mass (Da):41,064
Checksum:iEA352636D724D470
GO

Polymorphismi

Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIMi:609423].1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02006645L → V. Corresponds to variant dbSNP:rs4987052Ensembl.1
Natural variantiVAR_01433964V → I Confers relative resistance to infection by HIV-1; delay in disease progression in African Americans but not in Caucasians. 3 PublicationsCorresponds to variant dbSNP:rs1799864Ensembl.1
Natural variantiVAR_014340355G → E1 PublicationCorresponds to variant dbSNP:rs3918387Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001893314 – 374SLFHI…DKEGA → RYLSVFFRKHITKRFCKQCP VFYRETVDGVTSTNTPSTGE QEVSAGL in isoform B. 2 PublicationsAdd BLAST61

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U03882 mRNA. Translation: AAA19119.1.
U03905 mRNA. Translation: AAA19120.1.
D29984 mRNA. Translation: BAA06253.1.
U80924 Genomic DNA. Translation: AAC51637.1.
U80924 Genomic DNA. Translation: AAC51636.1.
AF545480 Genomic DNA. Translation: AAN16400.1.
AK292685 mRNA. Translation: BAF85374.1.
AK292920 mRNA. Translation: BAF85609.1.
U95626 Genomic DNA. Translation: AAB57791.1.
U95626 Genomic DNA. Translation: AAB57792.1.
CH471055 Genomic DNA. Translation: EAW64760.1.
BC074751 mRNA. Translation: AAH74751.1.
BC095540 mRNA. Translation: AAH95540.1.
BC126452 mRNA. Translation: AAI26453.1.
BC136396 mRNA. Translation: AAI36397.1.
X95583 mRNA. Translation: CAA64835.1.
CCDSiCCDS43078.1. [P41597-1]
CCDS46813.1. [P41597-2]
PIRiI38450.
JC2443.
RefSeqiNP_001116513.2. NM_001123041.2. [P41597-1]
NP_001116868.1. NM_001123396.1. [P41597-2]
XP_011532371.1. XM_011534069.1. [P41597-2]
UniGeneiHs.511794.
Hs.705362.

Genome annotation databases

EnsembliENST00000292301; ENSP00000292301; ENSG00000121807. [P41597-1]
ENST00000400888; ENSP00000383681; ENSG00000121807. [P41597-1]
ENST00000445132; ENSP00000399285; ENSG00000121807. [P41597-2]
GeneIDi729230.
KEGGihsa:729230.
UCSCiuc003cpm.5. human. [P41597-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCCR2_HUMAN
AccessioniPrimary (citable) accession number: P41597
Secondary accession number(s): A0AVQ3
, B2RMT0, O95950, Q4VBL2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 22, 2017
This is version 182 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, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  8. SIMILARITY comments
    Index of protein domains and families