This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this recept... See more...

Aliases for ACKR2 Gene

Aliases for ACKR2 Gene

  • Atypical Chemokine Receptor 2 2 3 4 5
  • Chemokine-Binding Protein D6 3 4
  • Chemokine-Binding Protein 2 3 4
  • Chemokine Receptor CCR-10 3 4
  • C-C Chemokine Receptor D6 3 4
  • Chemokine Receptor CCR-9 3 4
  • CMKBR9 3 4
  • CCBP2 3 4
  • CCR10 3 4
  • D6 3 4
  • CC-Chemokine-Binding Receptor JAB61 3
  • Chemokine (C-C Motif) Receptor 9 3
  • Chemokine Binding Protein 2 2
  • Chemokine (C-C) Receptor 9 3
  • Chemokine Receptor D6 3
  • CCR9 3
  • HD6 3

External Ids for ACKR2 Gene

Previous HGNC Symbols for ACKR2 Gene

  • CMKBR9
  • CCBP2

Previous GeneCards Identifiers for ACKR2 Gene

  • GC03P042846

Summaries for ACKR2 Gene

Entrez Gene Summary for ACKR2 Gene

  • This gene encodes a beta chemokine receptor, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. Chemokines and their receptor-mediated signal transduction are critical for the recruitment of effector immune cells to the inflammation site. This gene is expressed in a range of tissues and hemopoietic cells. The expression of this receptor in lymphatic endothelial cells and overexpression in vascular tumors suggested its function in chemokine-driven recirculation of leukocytes and possible chemokine effects on the development and growth of vascular tumors. This receptor appears to bind the majority of beta-chemokine family members; however, its specific function remains unknown. This gene is mapped to chromosome 3p21.3, a region that includes a cluster of chemokine receptor genes. [provided by RefSeq, Jul 2008]

GeneCards Summary for ACKR2 Gene

ACKR2 (Atypical Chemokine Receptor 2) is a Protein Coding gene. Diseases associated with ACKR2 include Testicular Leukemia and Cd45 Deficiency. Among its related pathways are Peptide ligand-binding receptors and Chemokine Superfamily Pathway: Human/Mouse Ligand-Receptor Interactions. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and chemokine receptor activity. An important paralog of this gene is CCR1.

UniProtKB/Swiss-Prot Summary for ACKR2 Gene

  • Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.

Gene Wiki entry for ACKR2 Gene

Additional gene information for ACKR2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ACKR2 Gene

Genomics for ACKR2 Gene

GeneHancer (GH) Regulatory Elements for ACKR2 Gene

Promoters and enhancers for ACKR2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ACKR2 on UCSC Golden Path with GeneCards custom track

Genomic Locations for ACKR2 Gene

Genomic Locations for ACKR2 Gene
chr3:42,804,752-42,887,974
(GRCh38/hg38)
Size:
83,223 bases
Orientation:
Plus strand
chr3:42,846,244-42,929,466
(GRCh37/hg19)
Size:
83,223 bases
Orientation:
Plus strand

Genomic View for ACKR2 Gene

Genes around ACKR2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ACKR2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ACKR2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ACKR2 Gene

Proteins for ACKR2 Gene

  • Protein details for ACKR2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00590-ACKR2_HUMAN
    Recommended name:
    Atypical chemokine receptor 2
    Protein Accession:
    O00590
    Secondary Accessions:
    • B2R8Y8
    • O00537
    • Q53YA1
    • Q86UN9
    • Q96A02

    Protein attributes for ACKR2 Gene

    Size:
    384 amino acids
    Molecular mass:
    43443 Da
    Quaternary structure:
    No Data Available

neXtProt entry for ACKR2 Gene

Post-translational modifications for ACKR2 Gene

  • Phosphorylated on serine residues in the C-terminal cytoplasmic tail.
  • Glycosylation at Asn19
  • Modification sites at PhosphoSitePlus

Other Protein References for ACKR2 Gene

Antibody Products

No data available for DME Specific Peptides for ACKR2 Gene

Domains & Families for ACKR2 Gene

Gene Families for ACKR2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • G-protein coupled receptors
  • Predicted membrane proteins

Protein Domains for ACKR2 Gene

Suggested Antigen Peptide Sequences for ACKR2 Gene

GenScript: Design optimal peptide antigens:
  • Chemokine-binding protein D6 (CCBP2_HUMAN)
  • Chemokine receptor D6 (Q7Z7I1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O00590

UniProtKB/Swiss-Prot:

ACKR2_HUMAN :
  • The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.
  • Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
Domain:
  • The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.
Family:
  • Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
genes like me logo Genes that share domains with ACKR2: view

Function for ACKR2 Gene

Molecular function for ACKR2 Gene

UniProtKB/Swiss-Prot Function:
Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.
UniProtKB/Swiss-Prot Induction:
By interleukin-6 and interferon-gamma.

Phenotypes From GWAS Catalog for ACKR2 Gene

Gene Ontology (GO) - Molecular Function for ACKR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004950 chemokine receptor activity IEA,TAS 9364936
GO:0005044 scavenger receptor activity IMP,IEA 23633677
GO:0016493 C-C chemokine receptor activity IBA 21873635
GO:0019956 chemokine binding IBA 21873635
GO:0019957 C-C chemokine binding IBA,IEA 21873635
genes like me logo Genes that share ontologies with ACKR2: view
genes like me logo Genes that share phenotypes with ACKR2: view

Animal Models for ACKR2 Gene

MGI Knock Outs for ACKR2:

Animal Model Products

  • Taconic Biosciences Mouse Models for ACKR2

CRISPR Products

miRNA for ACKR2 Gene

miRTarBase miRNAs that target ACKR2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ACKR2 Gene

Localization for ACKR2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ACKR2 Gene

Early endosome. Recycling endosome. Cell membrane; Multi-pass membrane protein. Note=Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via clathrin-coated pits. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ACKR2 gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
endosome 5
nucleus 4
cytosol 4
extracellular 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Vesicles (3)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ACKR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005829 cytosol IDA --
GO:0005884 actin filament IDA 23633677
genes like me logo Genes that share ontologies with ACKR2: view

Pathways & Interactions for ACKR2 Gene

genes like me logo Genes that share pathways with ACKR2: view

Pathways by source for ACKR2 Gene

1 BioSystems pathway for ACKR2 Gene

Gene Ontology (GO) - Biological Process for ACKR2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis IEA --
GO:0006935 chemotaxis IEA,IBA 21873635
GO:0006954 inflammatory response IEA --
GO:0006955 immune response IBA,TAS 21873635
GO:0007165 signal transduction IEA --
genes like me logo Genes that share ontologies with ACKR2: view

No data available for SIGNOR curated interactions for ACKR2 Gene

Drugs & Compounds for ACKR2 Gene

(1) Drugs for ACKR2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for ACKR2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ACKR2: view

Transcripts for ACKR2 Gene

mRNA/cDNA for ACKR2 Gene

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ACKR2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b · 6c ^ 7 ^ 8 ^ 9a · 9b · 9c · 9d
SP1:
SP2: - - - - - - - -
SP3:
SP4:
SP5: - -
SP6: - - - - - - - - -

Relevant External Links for ACKR2 Gene

GeneLoc Exon Structure for
ACKR2
ECgene alternative splicing isoforms for
ACKR2

Expression for ACKR2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ACKR2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ACKR2 Gene

This gene is overexpressed in Liver (x9.5) and Nerve - Tibial (x5.2).

Protein differential expression in normal tissues from HIPED for ACKR2 Gene

This gene is overexpressed in Placenta (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for ACKR2 Gene



Protein tissue co-expression partners for ACKR2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of ACKR2 Gene:

ACKR2

mRNA Expression by UniProt/SwissProt for ACKR2 Gene:

O00590-ACKR2_HUMAN
Tissue specificity: Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.

Evidence on tissue expression from TISSUES for ACKR2 Gene

  • Liver(4.4)
  • Lung(4.3)
  • Intestine(2.4)
  • Spleen(2.4)
  • Blood(2.3)
  • Lymph node(2.2)
genes like me logo Genes that share expression patterns with ACKR2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for ACKR2 Gene

Orthologs for ACKR2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ACKR2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CCBP2 32
  • 99.05 (n)
ACKR2 33
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ACKR2 33 32
  • 84.12 (n)
OneToOne
cow
(Bos Taurus)
Mammalia ACKR2 32
  • 80.62 (n)
CCBP2 33
  • 65 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ackr2 32
  • 76.73 (n)
mouse
(Mus musculus)
Mammalia Ackr2 17 33 32
  • 76.04 (n)
chicken
(Gallus gallus)
Aves CCBP2 32
  • 57.5 (n)
ACKR2 33
  • 43 (a)
OneToOne
Species where no ortholog for ACKR2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)
  • zebrafish (Danio rerio)

Evolution for ACKR2 Gene

ENSEMBL:
Gene Tree for ACKR2 (if available)
TreeFam:
Gene Tree for ACKR2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ACKR2: view image

Paralogs for ACKR2 Gene

(31) SIMAP similar genes for ACKR2 Gene using alignment to 5 proteins:

  • ACKR2_HUMAN
  • V9GYB7_HUMAN
  • V9GYM0_HUMAN
  • V9GYX0_HUMAN
  • V9GZ70_HUMAN
genes like me logo Genes that share paralogs with ACKR2: view

Variants for ACKR2 Gene

Sequence variations from dbSNP and Humsavar for ACKR2 Gene

SNP ID Clin Chr 03 pos Variation AA Info Type
rs1000040851 -- 42,854,503(+) T/C intron_variant
rs1000098697 -- 42,860,813(+) A/G intron_variant
rs1000107540 -- 42,856,119(+) A/G intron_variant
rs1000129818 -- 42,861,090(+) G/C intron_variant
rs1000145138 -- 42,844,082(+) G/A/T intron_variant

Structural Variations from Database of Genomic Variants (DGV) for ACKR2 Gene

Variant ID Type Subtype PubMed ID
esv22156 CNV loss 19812545
esv2725201 CNV deletion 23290073
esv2725202 CNV deletion 23290073
esv2725203 CNV deletion 23290073
esv3303650 CNV mobile element insertion 20981092
esv3307554 CNV mobile element insertion 20981092
esv3310360 CNV mobile element insertion 20981092
esv3339689 CNV insertion 20981092

Variation tolerance for ACKR2 Gene

Residual Variation Intolerance Score: 53.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.77; 47.12% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ACKR2 Gene

Human Gene Mutation Database (HGMD)
ACKR2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ACKR2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ACKR2 Gene

Disorders for ACKR2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for ACKR2 Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
testicular leukemia
cd45 deficiency
sezary's disease
  • sezary disease
- elite association - COSMIC cancer census association via MalaCards
Search ACKR2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ACKR2

genes like me logo Genes that share disorders with ACKR2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ACKR2 Gene

Publications for ACKR2 Gene

  1. The beta-chemokine receptor D6 is expressed by lymphatic endothelium and a subset of vascular tumors. (PMID: 11238036) Nibbs RJ … Rot A (The American journal of pathology 2001) 3 4 23 56
  2. Cloning and characterization of a novel promiscuous human beta-chemokine receptor D6. (PMID: 9405404) Nibbs RJ … Graham GJ (The Journal of biological chemistry 1997) 2 3 4 56
  3. Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3. (PMID: 9364936) Bonini JA … Steiner DF (DNA and cell biology 1997) 2 3 4 56
  4. An analysis of the function and expression of D6 on lymphatic endothelial cells. (PMID: 23479571) McKimmie CS … Graham GJ (Blood 2013) 3 4 56
  5. β-arrestin-dependent activation of the cofilin pathway is required for the scavenging activity of the atypical chemokine receptor D6. (PMID: 23633677) Borroni EM … Locati M (Science signaling 2013) 3 4 56

Products for ACKR2 Gene

Sources for ACKR2 Gene