ACKR4 Gene (Protein Coding)

Atypical Chemokine Receptor 4

GC03P132597
GIFtS:
35
The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same prote... See more...

Aliases for ACKR4 Gene

Aliases for ACKR4 Gene

  • Atypical Chemokine Receptor 4 2 3 4 5
  • CCBP2 2 3 4
  • CCR11 2 3 4
  • VSHK1 2 3 4
  • Chemokine (C-C Motif) Receptor-Like 1 2 3
  • C-C Chemokine Receptor Type 11 3 4
  • CC Chemokine Receptor-Like 1 3 4
  • C-C CKR-11 3 4
  • CC-CKR-11 3 4
  • CCX CKR 3 4
  • CCX-CKR 2 3
  • CCR-11 3 4
  • CCRL1 3 4
  • PPR1 2 3
  • Orphan Seven-Transmembrane Receptor, Chemokine Related 3
  • Chemokine, Cc Motif, Receptor-Like Protein 1 3
  • Chemocentryx Chemokine Receptor 3
  • CKR-11 3
  • CCR10 3
  • ACKR4 5

External Ids for ACKR4 Gene

Previous HGNC Symbols for ACKR4 Gene

  • CCRL1

Previous GeneCards Identifiers for ACKR4 Gene

  • GC03P132317

Summaries for ACKR4 Gene

Entrez Gene Summary for ACKR4 Gene

  • The protein encoded by this gene is a member of the G protein-coupled receptor family, and is a receptor for C-C type chemokines. This receptor has been shown to bind dendritic cell- and T cell-activated chemokines including CCL19/ELC, CCL21/SLC, and CCL25/TECK. A pseudogene of this gene is found on chromosome 6. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2013]

GeneCards Summary for ACKR4 Gene

ACKR4 (Atypical Chemokine Receptor 4) is a Protein Coding gene. Diseases associated with ACKR4 include Irritant Dermatitis and Sezary's Disease. Among its related pathways are Signaling by GPCR and PEDF Induced Signaling. 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 CCR7.

UniProtKB/Swiss-Prot Summary for ACKR4 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 CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus.

Gene Wiki entry for ACKR4 Gene

Additional gene information for ACKR4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ACKR4 Gene

Genomics for ACKR4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Download GeneHancer 2017 data
Promoters and enhancers for ACKR4 Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH03J132596 Promoter/Enhancer 0.8 EPDnew Ensembl ENCODE 600.7 +0.3 331 1.6 ACKR4 NPHP3 piR-58929-068 UBA5 ACAD11 NPHP3-ACAD11
GH03J132540 Enhancer 0.9 FANTOM5 ENCODE 10.8 -54.6 -54557 3.5 JUND IKZF2 JUN NR2C2 FOS ZNF217 TFDP1 FOSL1 FOSL2 SAP130 UBA5 ACKR4 NPHP3 DNAJC13 piR-52438-082
GH03J132535 Enhancer 0.8 Ensembl ENCODE 10.6 -60.9 -60878 1.6 CTCF REST RAD21 ZNF24 TRIM22 MGA ZSCAN29 SMC3 EP400 MNT UBA5 ACAD11 ACKR4 DNAJC13 piR-52438-082
GH03J132553 Enhancer 0.7 Ensembl ENCODE 11.7 -41.6 -41648 4 ZNF24 SOX6 MNT CEBPB VEZF1 RXRA IKZF1 ACAD11 ACKR4 UBA5 DNAJC13 piR-52438-082
GH03J132569 Enhancer 0.7 Ensembl ENCODE dbSUPER 11.2 -28.0 -27980 1.5 ZNF316 MAFK DNAJC13 ACKR4 NPHP3 ACAD11 piR-52438-082 NPHP3-ACAD11
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ACKR4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ACKR4

Genomic Locations for ACKR4 Gene

Genomic Locations for ACKR4 Gene
chr3:132,597,270-132,618,967
(GRCh38/hg38)
Size:
21,698 bases
Orientation:
Plus strand
chr3:132,316,081-132,337,811
(GRCh37/hg19)
Size:
21,731 bases
Orientation:
Plus strand

Genomic View for ACKR4 Gene

Genes around ACKR4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ACKR4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ACKR4 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for ACKR4 Gene

Proteins for ACKR4 Gene

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  • Protein details for ACKR4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9NPB9-ACKR4_HUMAN
    Recommended name:
    Atypical chemokine receptor 4
    Protein Accession:
    Q9NPB9
    Secondary Accessions:
    • B2R9U7

    Protein attributes for ACKR4 Gene

    Size:
    350 amino acids
    Molecular mass:
    39914 Da
    Quaternary structure:
    • Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2.

neXtProt entry for ACKR4 Gene

Post-translational modifications for ACKR4 Gene

  • The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.
  • Glycosylation at Asn6 and Asn19
  • Modification sites at PhosphoSitePlus

Other Protein References for ACKR4 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for ACKR4 Gene

Domains & Families for ACKR4 Gene

Gene Families for ACKR4 Gene

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

Protein Domains for ACKR4 Gene

InterPro:
Blocks:
  • Chemokine receptor signature
  • C-C chemokine receptor type 11 signature
ProtoNet:

Suggested Antigen Peptide Sequences for ACKR4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ57069, highly similar to C-C chemokine receptor type 11 (B4E2W5_HUMAN)
  • CCX CKR (CCRL1_HUMAN)
  • CCRL1 protein (Q4VBN4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9NPB9

UniProtKB/Swiss-Prot:

ACKR4_HUMAN :
  • Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
Family:
  • Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
genes like me logo Genes that share domains with ACKR4: view

Function for ACKR4 Gene

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Molecular function for ACKR4 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 CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus.

Phenotypes From GWAS Catalog for ACKR4 Gene

Gene Ontology (GO) - Molecular Function for ACKR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004930 G protein-coupled receptor activity IEA --
GO:0004950 chemokine receptor activity IDA 23341447
GO:0005044 scavenger receptor activity IEA --
GO:0005515 protein binding IPI 23341447
GO:0016493 C-C chemokine receptor activity IBA 21873635
genes like me logo Genes that share ontologies with ACKR4: view
genes like me logo Genes that share phenotypes with ACKR4: view

Animal Models for ACKR4 Gene

MGI Knock Outs for ACKR4:

Animal Model Products

  • Taconic Biosciences Mouse Models for ACKR4

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ACKR4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for ACKR4 Gene

Localization for ACKR4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ACKR4 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 caveolae. 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 ACKR4 gene
Compartment Confidence
plasma membrane 5
endosome 3
extracellular 2
nucleus 2
cytoskeleton 1
mitochondrion 1
endoplasmic reticulum 1
cytosol 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Vesicles (3)
  • Mitochondria (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ACKR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005768 endosome IEA --
GO:0005769 early endosome IEA --
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane TAS 10767544
genes like me logo Genes that share ontologies with ACKR4: view

Pathways & Interactions for ACKR4 Gene

genes like me logo Genes that share pathways with ACKR4: view

Gene Ontology (GO) - Biological Process for ACKR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006897 endocytosis IEA --
GO:0006935 chemotaxis IBA 21873635
GO:0006955 immune response TAS,IBA 21873635
GO:0007165 signal transduction IEA --
GO:0007186 G protein-coupled receptor signaling pathway TAS,IEA --
genes like me logo Genes that share ontologies with ACKR4: view

No data available for SIGNOR curated interactions for ACKR4 Gene

Drugs & Compounds for ACKR4 Gene

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  1. Drug

(4) Drugs for ACKR4 Gene - From: DGIdb, IUPHAR, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
CCL19 Pharma Agonist, Full agonist, Unknown 0
CCL21 Pharma Agonist, Full agonist 0
CCL25 Pharma Agonist, Full agonist 0

(1) Additional Compounds for ACKR4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ACKR4: view

Transcripts for ACKR4 Gene

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  1. CRISPR
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  3. Inhibitory RNA
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mRNA/cDNA for ACKR4 Gene

2 REFSEQ mRNAs :
8 NCBI additional mRNA sequence :
2 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ACKR4

Alternative Splicing Database (ASD) splice patterns (SP) for ACKR4 Gene

No ASD Table

Relevant External Links for ACKR4 Gene

GeneLoc Exon Structure for
ACKR4

Expression for ACKR4 Gene

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  1. Primer
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mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ACKR4 Gene

mRNA expression in normal human tissues for ACKR4 Gene
mRNA expression by BioGPS for ACKR4 GenemRNA expression by GTEx for ACKR4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ACKR4

mRNA Expression by UniProt/SwissProt for ACKR4 Gene:

Q9NPB9-ACKR4_HUMAN
Tissue specificity: Predominantly expressed in heart. Lower expression in lung, pancreas, spleen, colon, skeletal muscle and small intestine.

Evidence on tissue expression from TISSUES for ACKR4 Gene

  • Intestine(2.6)
  • Spleen(2.5)
  • Skin(2.5)
  • Blood(2.5)
  • Lymph node(2.4)
  • Liver(2.2)
  • Heart(2.1)
  • Lung(2.1)
  • Bone marrow(2)
genes like me logo Genes that share expression patterns with ACKR4: view

No data available for mRNA differential expression in normal tissues , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for ACKR4 Gene

Orthologs for ACKR4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for ACKR4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
 Mammalia CCRL1 30 31
  • 99.43 (n)
 OneToOne
Cow
(Bos Taurus)
 Mammalia ACKR4 30
  • 88.38 (n)
CCRL1 31
  • 86 (a)
 OneToOne
Dog
(Canis familiaris)
 Mammalia ACKR4 30 31
  • 88.29 (n)
 OneToOne
Mouse
(Mus musculus)
 Mammalia Ackr4 30 17 31
  • 83.33 (n)
 OneToOne
Rat
(Rattus norvegicus)
 Mammalia Ackr4 30
  • 82.95 (n)
Oppossum
(Monodelphis domestica)
 Mammalia ACKR4 31
  • 77 (a)
 OneToOne
Platypus
(Ornithorhynchus anatinus)
 Mammalia ACKR4 31
  • 70 (a)
 OneToOne
Chicken
(Gallus gallus)
 Aves CCRL1 30
  • 65.89 (n)
ACKR4 31
  • 59 (a)
 OneToOne
Lizard
(Anolis carolinensis)
 Reptilia ACKR4 31
  • 56 (a)
 OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
 Amphibia ccrl1 30
  • 62.5 (n)
Zebrafish
(Danio rerio)
 Actinopterygii si:ch211-106h4.12 30
  • 56.8 (n)
ackr4a 31
  • 44 (a)
 OneToMany
ackr4b 31
  • 41 (a)
 OneToMany
Species where no ortholog for ACKR4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium 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)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (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)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ACKR4 Gene

ENSEMBL:
Gene Tree for ACKR4 (if available)
TreeFam:
Gene Tree for ACKR4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ACKR4: view image

Paralogs for ACKR4 Gene

Paralogs for ACKR4 Gene

(31) SIMAP similar genes for ACKR4 Gene using alignment to 2 proteins:

  • ACKR4_HUMAN
  • H0Y9Z2_HUMAN
genes like me logo Genes that share paralogs with ACKR4: view

Variants for ACKR4 Gene

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Additional dbSNP identifiers (rs#s) for ACKR4 Gene

Structural Variations from Database of Genomic Variants (DGV) for ACKR4 Gene

Variant ID Type Subtype PubMed ID
nsv979879 CNV duplication 23825009

Variation tolerance for ACKR4 Gene

Residual Variation Intolerance Score: 73.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.30; 25.84% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ACKR4 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ACKR4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ACKR4 Gene

Disorders for ACKR4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for ACKR4 Gene - From: DISEASES

Disorder Aliases PubMed IDs
irritant dermatitis
  • irritant contact dermatitis
sezary's disease
  • sezary disease
- elite association - COSMIC cancer census association via MalaCards
Search ACKR4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ACKR4

ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
genes like me logo Genes that share disorders with ACKR4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ACKR4 Gene

Publications for ACKR4 Gene

  1. Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR. (PMID: 11981810) Townson JR … Nibbs RJ (European journal of immunology 2002) 3 4 23
  2. Cloning of CCRL1, an orphan seven transmembrane receptor related to chemokine receptors, expressed abundantly in the heart. (PMID: 10767544) Khoja H … Shyamala V (Gene 2000) 2 3 4
  3. Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK. (PMID: 10706668) Gosling J … Schall TJ (Journal of immunology (Baltimore, Md. : 1950) 2000) 3 4 23
  4. β-Arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR. (PMID: 23341447) Watts AO … Vischer HF (The Journal of biological chemistry 2013) 3 4
  5. Inhibition of CXCR3-mediated chemotaxis by the human chemokine receptor-like protein CCX-CKR. (PMID: 23121557) Vinet J … Boddeke HW (British journal of pharmacology 2013) 3 4

ExternalLinks

View latest publications for ACKR4 gene in Mastermind

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