Recombinant Human Atypical Chemokine Receptor 1 (ACKR1) Protein (His), Active

Name: Recombinant Human Atypical Chemokine Receptor 1 (ACKR1) Protein (His), Active
Brand: Beta LifeScience
SKU: BLC-05636P
Availability: InStock

Activity Measured by its binding ability in a functional ELISA. Immobilized ACKR1 at 1 μg/ml can bind human CCL2, the EC 50 of human CCL2 protein is 48.64-60.24 μg/ml.

Greater than 85% as determined by SDS-PAGE.

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Product Overview

Description	Recombinant Human Atypical Chemokine Receptor 1 (ACKR1) Protein (His), Active is produced by our E.coli expression system. This is a full length protein.
Purity	Greater than 85% as determined by SDS-PAGE.
Activity	Measured by its binding ability in a functional ELISA. Immobilized ACKR1 at 1 μg/ml can bind human CCL2, the EC50 of human CCL2 protein is 48.64-60.24 μg/ml.
Uniprotkb	Q16570
Target Symbol	ACKR1
Synonyms	ACKR1; DARC; FY; GPD; Atypical chemokine receptor 1; Duffy antigen/chemokine receptor; Fy glycoprotein; GpFy; Glycoprotein D; Plasmodium vivax receptor; CD antigen CD234
Species	Homo sapiens (Human)
Expression System	in vitro E.coli expression system
Tag	N-10His
Target Protein Sequence	MGNCLHRAELSPSTENSSQLDFEDVWNSSYGVNDSFPDGDYGANLEAAAPCHSCNLLDDSALPFFILTSVLGILASSTVLFMLFRPLFRWQLCPGWPVLAQLAVGSALFSIVVPVLAPGLGSTRSSALCSLGYCVWYGSAFAQALLLGCHASLGHRLGAGQVPGLTLGLTVGIWGVAALLTLPVTLASGASGGLCTLIYSTELKALQATHTVACLAIFVLLPLGLFGAKGLKKALGMGPGPWMNILWAWFIFWWPHGVVLGLDFLVRSKLLLLSTCLAQQALDLLLNLAEALAILHCVATPLLLALFCHQATRTLLPSLPLPEGWSSHLDTLGSKS
Expression Range	1-336aa
Protein Length	Full Length
Mol. Weight	41.1 kDa
Research Area	Cardiovascular
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target 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. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
Subcellular Location	Early endosome. Recycling endosome. 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.
Protein Families	G-protein coupled receptor 1 family, Atypical chemokine receptor subfamily
Database References	HGNC: 4035 OMIM: 110700 KEGG: hsa:2532 STRING: 9606.ENSP00000357103 UniGene: PMID: 30257710 The atypical chemokine receptor 1 polymorphism (rs12075) does not affect susceptibility to hepatitis C virus. PMID: 28443566 The risk of Plasmodium vivax malaria associated with genetic variation of DARC in Thai patients is reported. PMID: 29620340 Our findings in mice suggest that DARC alters the severity and resolution of AHR. These findings are complimented by our human analyses in which select DARC SNPs are associated with worse asthma control and symptoms. PMID: 28471517 DARC expression in cancer cells inhibits pancreatic ductal adenocarcinoma progression by suppressing STAT3 activation through the inhibition of CXCR2 signaling PMID: 28214673 This study reports 1-3 occurrences of P. vivax infection in each of 25 Duffy-negative children at six time points over two rainy seasons and the beginning of the third season. PMID: 28749772 Data suggest that Type II congenital smell loss patients who exhibit both type I hyposmia and hypogeusia are genetically distinct from all other patients with Type II congenital smell loss. This distinction is based on decreased Fy(b) expression which correlated with abnormalities in two sensory modalities (hyposmia type I and hypogeusia). PMID: 27968956 The data suggest that selective exposure of the Duffy binding protein (DBP) binding site within DARC is key to the preferential binding of DBP to immature reticulocytes, which is the potential mechanism underlying the preferential infection of a reticulocyte subset by P vivax. PMID: 28754683 ACKR1 regulates neutrophil counts in blood. Lack of ACKR1 on nucleated erythroid cells together with its expression in endothelial cells causes neutropenia. PMID: 28553950 population genetic analysis of DARC shows its association with malaria resistance PMID: 28282382 Molecular identification of rare FYNull and FYX alleles in Caucasian thalassemic family from Sardinia. PMID: 25921504 We showed that DARC expression is down-regulated in CRC and associated with clinical pathological features and MVD of CRC. DARC might be involved in tumorigenesis, progression, angiogenesis, and metastasis of CRC. PMID: 26096170 DARC is required for Staphylococcus aureus-mediated lysis of human erythrocytes, and DARC overexpression is sufficient to render cells susceptible to toxin-mediated lysis. PMID: 26320997 the odds for neutropenia in the ACKR1-null (FY-) individuals were 46-fold higher than for FY+ individuals (Crude odds ratio = 46, 95% confidence interval = 8.03-263, P < 0.001) PMID: 25817587 study demonstrates the association of SNP rs12075 from DARC gene with the levels of serum IL8 PMID: 25647274 DARC levels are elevated in human keloid fibroblasts and might inhibit the secretion of CCL2. PMID: 26045366 Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. PMID: 25582271 The majority of our population is heterozygous for Duffy antigens a and b. PMID: 24929836 Duffy blood group PMID: 24845979 Isothermal titration calorimetry studies show these structures are part of a multi-step binding pathway, and individual point mutations of residues contacting DARC result in a complete loss of RBC binding by DBP-RII. PMID: 24415938 DARC polymorphisms may influence the naturally acquired inhibitory anti-Duffy binding protein II immunity PMID: 24710306 DARC facilitates CXCL1 inhibition of airway smooth muscle cell migration via modulation of the ERK-1/2 MAP kinase signaling pathway. PMID: 24981451 The Fy(a-b-) phenotype in three siblings of the Polish family was caused by the FY()X/FY()B-33 genotype. PMID: 23820435 DARC antigen is associated with a likelihood for patients to develop leg ulcers in sickle cell disease. PMID: 23753024 Effect of genetic variants in two chemokine decoy receptor genes, DARC and CCBP2, on metastatic potential of breast cancer. PMID: 24260134 co-expression of DARC, D6, and CCX-CKR significantly associated with higher survival in gastric cancer PMID: 23462454 The in fl uence of DARC gene expression on bone mineral density of the mandible was not con fi rmed. PMID: 22910367 DARC and BCAM expression was associated with pathogenesis of thyroid carcinoma and correlated with clinical-pathological features. PMID: 23168236 The high frequency of the FYES allele that silences erythroid expression of the Duffy antigen offers a biologically plausible explanation for the lack of Plasmodium vivax infections observed. PMID: 23347639 Although lower, the risk of Duffy-negatives to experience a P. vivax blood stage infection was not significantly different to that of Duffy-positives. PMID: 23259672 strong associations between SNPs in DARC gene, particularly rs12075, and serum MCP-1 levels identify a potential candidate gene that can be explored for its role in inflammatory pathways; replication of European GWAS of MCP-1 in study of Hispanic children confirms importance of DARC in regulation of MCP-1 PMID: 23017229 vivax malaria incidences over the past five years in an Indian population were significantly negatively and positively associated with the frequencies of the FYA and FYB alleles of the Duffy gene, respectively. PMID: 23028857 platelet molecule platelet factor 4 (PF4 or CXCL4) and the erythrocyte Duffy-antigen receptor (Fy) are necessary for platelet-mediated killing of Plasmodium falciparum parasites. PMID: 23224555 Data suggest that DARC (Duffy antigen receptor for chemokines) gene may play an important role in regulating the metabolisms of both lean body mass (LBM) and age at menarche (AAM). PMID: 22744181 We developed a phylogenetic tree for DARC alleles and postulated a distinct FY*B allele as ancestral for the extant DARC alleles in humans. PMID: 22082243 Our results provide evidence that the functional rs2814778 polymorphism in the gene encoding DARC is associated with worse clinical outcomes among African Americans with ALI, possibly via an increase in circulating IL-8. PMID: 22207676 Data show that in ancestry to the African continent (AA) subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association with white blood cell count (WBC) levels. PMID: 22037903 findings show that Fy(a), compared with Fy(b), significantly diminishes binding of Pv Duffy binding protein (PvDBP) at the erythrocyte surface, and is associated with a reduced risk of clinical Plasmodium vivax in humans PMID: 22123959 It seems that this version of DARC receptor is a powerful facilitator of chemokine transcytosis and subsequently leukocyte migration into GVHD target organs. PMID: 21784153 Here we describe the recent success in mapping the gene that underlies benign neutropenia in African American populations. We discuss the known function of the gene and consider potential mechanisms for the effect on neutropenia.[review] PMID: 22097233 despite an association of CCL2 serum levels with the severity of liver fi brosis, a functional SNP in the CCL2 scavenger receptor DARC is not directly associated with the occurrence or the severity of liver disease in hepatitis C infection infection PMID: 21156192 DARC -46C/C results in loss of DARC expression on erthyrocytes (Duffy-null) and resistance to Plasmodium vivax malaria, and subjects with this genotype had pre-HIV seroconversion neutrophil counts of <2500 cells/mm(3). PMID: 21507922 DARC and D6, the most studied members of this group of molecules, are reviewed. PMID: 21151196 results do not support an effect of erythrocyte DARC expression on the risk or progression of prostate cancer in men of African descent. PMID: 20596779 This activation state associated with DARC RBC expression may influence the intensity of the inflammatory responses encountered in sickle cell anemia and participate in its interindividual clinical expression variability. PMID: 21088296 Duffy Antigen Receptor for Chemokines (DARC) is an unusual transmembrane chemokine receptor which binds the two main chemokine families. PMID: 20655787 Plasmodium vivax is able to infect and cause Malaria vivax in Duffy-negative people. PMID: 20655790 Results indicate that one of the primary mechanisms by which P. vivax evades host immunity is through DARC indirectly down-regulating humoral responses against erythrocytic invasion and development. PMID: 20664684 Genome-wide association analysis finds strong association for serum MCP-1 with a nonsynonymous polymorphism, rs12075 (Asp42Gly) in DARC. PMID: 20040767 Duffy-positive sickle cell anemia patients exhibited higher counts of white blood cells, polynuclear neutrophils, higher plasma levels of IL-8 and RANTES than Duffy-negative patients. PMID: 20347396

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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