Product Details

Target Names

ACKR2

Uniprot No.

O00590

Research Area

Immunology

Alternative Names

ACKR2; CCBP2; CCR10; CMKBR9; D6; Atypical chemokine receptor 2; C-C chemokine receptor D6; Chemokine receptor CCR-10; Chemokine receptor CCR-9; Chemokine-binding protein 2; Chemokine-binding protein D6

Species

Homo sapiens (Human)

Source

Mammalian cell

Expression Region

1-384aa

Target Protein Sequence

MAATASPQPLATEDADSENSSFYYYDYLDEVAFMLCRKDAVVSFGKVFLPVFYSLIFVLGLSGNLLLLMVLLRYVPRRRMVEIYLLNLAISNLLFLVTLPFWGISVAWHWVFGSFLCKMVSTLYTINFYSGIFFISCMSLDKYLEIVHAQPYHRLRTRAKSLLLATIVWAVSLAVSIPDMVFVQTHENPKGVWNCHADFGGHGTIWKLFLRFQQNLLGFLLPLLAMIFFYSRIGCVLVRLRPAGQGRALKIAAALVVAFFVLWFPYNLTLFLHTLLDLQVFGNCEVSQHLDYALQVTESIAFLHCCFSPILYAFSSHRFRQYLKAFLAAVLGWHLAPGTAQASLSSCSESSILTAQEEMTGMNDLGERQSENYPNKEDVGNKSA
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.

Tag Info

C-terminal 10xHis-tagged
If you have specified tag type, please tell us and we will check if it’s possible to develop.

Form

Lyophilized powder
Note: We will default ship it in lyophilized form with normal bule ice packs. However, if you request to ship in liquid form, it needs to be shipped with dry ice, please communicate with us in advance and extra fees for dry ice and dry ice box will be charged.

Buffer

Lyophilized from PBS, 6% Trehalose, pH 7.4

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Note: Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

Notes

Repeated freezing and thawing is not recommended. Store the protein at -20°C/-80°C upon receiving it, and ensure to avoid repeated freezing and thawing, otherwise, it will affect the protein activity.

Datasheet & COA

Please contact us to get it.

Target Background

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.

Gene References into Functions

Data suggest that MIRN146b and MIR10b directly bind 3'-untranslated region of ACKR2 and down-regulate expression of ACKR2 in keratinocytes and in lymphatic endothelial cells, respectively. (ACKR2 = atypical chemokine receptor 2) PMID: 29279330
ACKR2 is induced after traumatic brain injuries and has a significant impact on mortality and lesion development acutely following closed head injury. PMID: 29176798
ACKR2 is a molecular regulator play a role in inflammatory changes in patients with psoriasis. PMID: 28010760
Data indicates that D6 is concentrated on trophoblast cell membranes in pre-eclampsia, in line with higher circulating levels of D6-ligand chemokines, but its scavenging activity is affected by trophoblast cytoskeleton disarrangement. PMID: 27780270
ACKR2 mediates chemokine scavenging by primary human trophoblasts. PMID: 25297873
Data show the structural motifs in the atypical chemokine receptor 2 (ACKR2) are responsible for ligand binding, and suggest ACKR2-derived N-terminal peptides as being of potential therapeutic significance. PMID: 24644289
Data show that low decoy receptor D6 expression correlated to more invasive tumors and that tumor location influences D6 expression, which is lower in the more distal parts of the colon. PMID: 24013383
engagement of the ACR D6 by its ligands activates a beta-arrestin1-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin through the Rac1-PAK1-LIMK1 cascade. PMID: 23633677
co-expression of DARC, D6, and CCX-CKR significantly associated with higher survival in gastric cancer PMID: 23462454
D6, which is upregulated in both inflammatory and tumor contexts, is an essential regulator of inflammatory leukocyte interactions with lymphatic endothelial cells(LECs) and is required for immature/mature DC discrimination by LECs. PMID: 23479571
We here summarize the knowledge available today on D6 structural and signaling properties and its essential role for the control of inflammatory cells traffic and proper development of the adaptive immune response. PMID: 22939232
CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy. PMID: 22226505
D6 is expressed in AMs from patients with COPD, and its expression correlates with the degree of functional impairment and markers of immune activation. PMID: 22797410
These data demonstrate a novel role for D6 as a regulator of the transition from uninvolved to lesional skin in psoriasis. PMID: 22867710
Chemokine decoy receptor D6 limits CC-chemokine-dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction. PMID: 22796582
DARC and D6, the most studied members of this group of molecules, are reviewed. PMID: 21151196
Chemokne D6 expression is higher in biopsies taken from more severe cardiac allograft rejection. PMID: 20404785
D6 protein is found predominantly inside human choriocarcinoma-derived cells with only a small fraction available on the cell surface at any one time, yet it can progressively remove extracellular chemokines, without apparent desensitization. PMID: 20147628
CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments. PMID: 12406880
In lymphatic vessels D6 acts as a nonsignaling decoy receptor and scavenger for inflammatory CC chemokines, by clearing them and preventing excessive diffusion via afferent lymphatics to lymph nodes. PMID: 12594248
CCR10 and its mucosal epithelial ligand CCL28 have roles in the migration of circulating IgA plasmablasts PMID: 12671049
D6 is constitutively internalized via a ligand-independent, phosphorylation-independent association with beta-arrestin. PMID: 15084596
We also propose that lymphatic endothelial cell-expressed D6 might have a distinct but complementary role in restricting inflammatory leukocyte access to the lymphatic vasculature. PMID: 16814608
demonstrate the importance of proinflammatory CC chemokines in de novo tumorigenesis and reveal chemokine sequestration by D6 to be a novel and effective method of tumor suppression PMID: 17607362
the heptahelical body of D6 on its own can engage the endocytotic machinery of HEK293 cells but that the C terminus is indispensable for scavenging because it prevents initial chemokine engagement of D6 from inhibiting subsequent chemokine uptake. PMID: 18201974
Emphasis on two new players involved in regulating inflammation at the maternal-fetal interface: the long pentraxin PTX3 and the decoy receptor for inflammatory chemokines D6. PMID: 18676013
D6 plays a negative role in the growth and metastasis of breast cancer. PMID: 18708360
D6 expression is GATA1 dependent PMID: 18714007
Genetic variations are associated with liver inflammation in chronic hepatitis C PMID: 18822328
Immunohistochemistry on lung lymph nodes from patients with pulmonary tuberculosis showed that D6 expression was prominent in lymphatic endothelial cells, while CD68-positive macrophages did not stain for D6. PMID: 19446728
D6 cooperates with CD26 in the negative regulation of CCL14 by the selective degradation of its biologically active isoform. PMID: 19632987

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Subcellular Location

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.

Protein Families

G-protein coupled receptor 1 family, Atypical chemokine receptor subfamily

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. Als

Database Links

HGNC: 1565

OMIM: 602648

KEGG: hsa:1238

STRING: 9606.ENSP00000273145

UniGene: Hs.146346