Recombinant Human Corticotropin-releasing factor receptor 2 (CRHR2)
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Description
Signaling Mechanisms and Ligand Interactions
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Low ligand concentrations: Gαs-mediated cAMP/PKA pathway dominates, promoting metabolic and anti-inflammatory effects .
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High ligand concentrations: Recruitment of Gαi and β-Arrestin leads to receptor desensitization and alternative pathways like MAPK/ERK .
Endogenous Ligands:
Pharmacological Tools:
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Antisauvagine-30: Selective antagonist used to block CRHR2 in preclinical models .
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2,2′:5′,2′′:5′′,2′′′-Quaterthiophene: Small-molecule antagonist under investigation for heart failure .
Role in Metabolic Regulation
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Acute UCN2 treatment in mice induces insulin resistance via CRHR2-Gαs signaling, while chronic exposure desensitizes the receptor, restoring glucose tolerance .
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Phosphoproteomic analyses reveal UCN2-dependent phosphorylation of >200 proteins in skeletal muscle, including mTOR and PDK pathways linked to nutrient uptake .
Cardiovascular Implications
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Heart Failure:
| Intervention | Effect on Cardiac Function | Mechanism |
|---|---|---|
| Chronic UCN2 infusion | Reduced ejection fraction | cAMP/EPAC/CaMKII pathway activation |
| CRHR2 antagonist | Improved cardiac output | Suppression of CREB/MEF2 gene networks |
Neurological and Behavioral Roles
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CRHR2 modulates hypothalamic feeding circuits, with UCN2 suppressing Agrp (orexigenic) and enhancing Pomc (anorexigenic) gene expression .
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Knockout models exhibit anxiety-like behaviors and stress hypersensitivity, suggesting CNS-specific regulatory roles .
Therapeutic Applications and Clinical Relevance
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Heart Failure: CRHR2 antagonists show promise in preclinical models by blocking maladaptive cAMP signaling .
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Metabolic Disorders: Receptor desensitization strategies could mitigate insulin resistance in obesity .
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Cancer: CRHR2 overexpression in colon cancer correlates with enhanced cell adhesion and metastasis .
Research Tools and Recombinant Constructs
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siRNA/shRNA: Commercially available constructs (e.g., MISSION esiRNA) for gene silencing in murine and human models .
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Antibodies: Validated tools for Western blot (e.g., SAB4500466) and immunohistochemistry (e.g., HPA046683) .
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Recombinant Proteins: Expressed in systems like HEK293 cells for ligand-binding assays and structural studies .
Product Specs
Form
Lyophilized powder
Note: We prioritize shipping the format currently in stock. However, if you have specific format requirements, please specify them in your order remarks. We will fulfill your request if possible.
Note: We prioritize shipping the format currently in stock. However, if you have specific format requirements, please specify them in your order remarks. We will fulfill your request if possible.
Lead Time
Delivery time may vary depending on the purchase method and location. Please contact your local distributors for specific delivery timelines.
Note: All protein shipments include standard blue ice packs. If you require dry ice packaging, please inform us in advance as additional fees may apply.
Note: All protein shipments include standard blue ice packs. If you require dry ice packaging, please inform us in advance as additional fees may apply.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
We recommend briefly centrifuging this vial prior to opening to ensure the contents settle at the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. We suggest adding 5-50% glycerol (final concentration) and aliquoting for long-term storage at -20°C/-80°C. Our default glycerol concentration is 50% and can serve as a reference.
Shelf Life
Shelf life is influenced by multiple factors, including storage conditions, buffer components, temperature, and protein stability.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. Lyophilized form has a shelf life of 12 months at -20°C/-80°C.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. Lyophilized form has a shelf life of 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquot for multiple uses to avoid repeated freeze-thaw cycles.
Tag Info
Tag type is determined during the manufacturing process.
The tag type will be determined during production. If you have a specific tag type in mind, please inform us, and we will prioritize developing it for you.
Synonyms
CRHR2; CRF2R; CRH2R; Corticotropin-releasing factor receptor 2; CRF-R-2; CRF-R2; CRFR-2; Corticotropin-releasing hormone receptor 2; CRH-R-2; CRH-R2
Buffer Before Lyophilization
Tris/PBS-based buffer, 6%
Trehalose.
Datasheet
Please contact us to get it.
Expression Region
1-411
Protein Length
Full Length Protein
Species
Homo sapiens (Human)
Target Names
Target Protein Sequence
MDAALLHSLLEANCSLALAEELLLDGWGPPLDPEGPYSYCNTTLDQIGTCWPRSAAGALVERPCPEYFNGVKYNTTRNAYRECLENGTWASKINYSQCEPILDDKQRKYDLHYRIALVVNYLGHCVSVAALVAAFLLFLALRSIRCLRNVIHWNLITTFILRNVMWFLLQLVDHEVHESNEVWCRCITTIFNYFVVTNFFWMFVEGCYLHTAIVMTYSTERLRKCLFLFIGWCIPFPIIVAWAIGKLYYENEQCWFGKEPGDLVDYIYQGPIILVLLINFVFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLLGITYMLFFVNPGEDDLSQIMFIYFNSFLQSFQGFFVSVFYCFFNGEVRSAVRKRWHRWQDHHSLRVPMARAMSIPTSPTRISFHSIKQTAAV
Uniprot No.
Target Background
Function
Corticotropin-releasing hormone receptor 2 (CRHR2) is a G-protein coupled receptor that binds to corticotropin-releasing factor (CRH), urocortin (UCN), UCN2, and UCN3. It exhibits high affinity for UCN. Ligand binding induces a conformational change that triggers signaling through guanine nucleotide-binding proteins (G proteins) and downstream effectors, such as adenylate cyclase. This activation promotes adenylate cyclase activity, resulting in increased intracellular cAMP levels.
Gene References Into Functions
- A non-coding CRHR2 SNP rs255105, a cis-eQTL for a downstream lincRNA AC005154.6, is associated with heroin addiction. PMID: 29953524
- CRF2 signaling induces alterations in both epithelial permeability and the differentiation of human colonic carcinoma cell lines. PMID: 28811708
- Data indicate that corticotropin releasing hormone receptor 2 (Crhr2) protein is abundantly expressed in the heart, and plasma Ucn2 levels were higher in patients with heart failure compared to healthy controls, suggesting that endogenous Crhr2 is associated with heart failure. PMID: 28550160
- Our findings indicate that sex shows significant interaction with genotype and Ucn1 during colitis. Human duodenal and colonic biopsies revealed sex-specific differences in levels of CRF receptors and Ucn1 expression in patients with Crohn's disease (CD) compared with matched non-IBD subjects. Notably, Ucn1 mediates sex-specific immune and cellular signaling responses via CRF2, highlighting the need for inclusive research considerations. PMID: 27053649
- Endogenous CRF may be involved in the pathogenesis of ischemia/reperfusion-induced enteritis, possibly via the activation of peripheral CRF receptor 2. PMID: 28011950
- This study demonstrated associations between two CRHR2 variants (rs4722999-C and rs12701020-C) and borderline personality disorder (BPD) in individuals with a history of sexual and physical abuse. PMID: 26182893
- Research has identified associations between CRHR2 genotypes and haplotypes and negative emotions in irritable bowel syndrome (IBS) patients and controls. PMID: 26808377
- Wound healing and signal transducer and activator of transcription 3 activity were elevated in CRHR2-overexpressing cells after urocortin 2 and IL-6 treatment, suggesting enhanced healing progression. PMID: 26597886
- This study demonstrated that CRF2 Receptor Deficiency Eliminates the Long-Lasting Vulnerability of Motivational States Induced by Opiate Withdrawal. PMID: 25672976
- D1 and CRF2 alpha receptors are capable of heterodimerization in living cells. D1/CRF2 alpha receptor heteromerization might contribute to the complex physiological interactions between dopamine and CRH. PMID: 25073922
- No significant difference in placental expression was observed between intrahepatic cholestasis of pregnancy and controls. PMID: 25172671
- CRHR2 was not up-regulated by labor in placenta, fetal membranes, or myometrium. PMID: 25426872
- The HSF2 element confers estrogen up-regulation of CRHR2 transcription, and estrogen increases CRHR2 transcription through induction of HSF2 demethylation. PMID: 24485608
- Results suggest that CRHR-2 variants may affect the risk for post-traumatic stress disorder (PTSD) in women by attenuating the stress response and reducing symptom severity. PMID: 24123648
- The rate and extent of homologous CRF2(a) receptor desensitization are influenced by agonist-specific mechanisms affecting G protein-coupled receptor kinase phosphorylation. PMID: 23820308
- CRFR2 antagonist astressin-2B abrogated the effects of UCN2 on vascular smooth muscle cells (VSMCs). This finding suggests that UCN2 is significantly associated with abdominal aortic aneurysm (AAA) and inhibits VSMC proliferation by inducing a G1 cell cycle arrest, implying a possible regulatory role in AAA pathogenesis. PMID: 24107226
- The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of ulcerative colitis patients indicates a change in CRF2 signaling associated with the inflammatory process. PMID: 23539366
- Polymorphisms within CRHR1 and CRHR2 genes interacted with both childhood sexual abuse and emotional neglect to influence Iowa Gambling Task performance. PMID: 23177644
- Evidence suggests that urocortin 1 increases lipopolysaccharide (LPS)-induced endothelial permeability by disrupting the VE-cadherin-beta-catenin complex via activation of CRHR2. PMID: 23168683
- These findings reveal a complex interplay between signaling molecules that allow fine-tuning of CRH-R2beta functional responses and regulate signal integration. PMID: 21338628
- Nuclear translocation of Ucn along with the loss of CRFR2 in epithelial cells and microvasculature of tumor specimens may be involved in the pathobiology of renal cell carcinoma. PMID: 19437022
- Trophoblast cell cultures treated with increasing amounts of type 2 corticotrophin releasing hormone receptor mediate increased secretion of estradiol in the presence of androstenedione. PMID: 19417223
- Structural basis for hormone recognition by the Human CRFR2{alpha} G protein-coupled receptor. PMID: 20966082
- There is no significant difference between the expression of CRH-R2beta mRNA of preeclampsia and of normal pregnancies. PMID: 15924674
- Research investigated whether a genetic variation in the CRHR2 gene might be associated with preterm birth. The polymorphism does not increase the risk for preterm birth overall but might modulate the length of pregnancy in a dose-dependent manner in Caucasian women. PMID: 20164545
- Results suggest that the rs2267716 polymorphism in the CRHR2 gene might influence the risk of developing hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection in the Chinese population. PMID: 19813023
- Data suggest a distinctive role for corticotropin-releasing hormone receptor 2-specific agonists like urocortin II in regulating myometrial contractility during human pregnancy. PMID: 14592950
- The regions of the CRF2(a) promoter that regulate inducible expression were determined. PMID: 15331578
- Ligand binding properties of CRFR2 were investigated. PMID: 15652653
- Expression by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and fluorescent immunocytochemistry was examined in umbilical cord blood-derived cultured mast cells. PMID: 16326828
- The examined CRHR2 polymorphisms do not confer susceptibility to panic disorder. PMID: 16691126
- Results demonstrate corticotropin-releasing factor (2) expression in the human gastric mucosa and indicate a physiological role of this receptor type in regulating apoptosis, a crucial parameter in gastric cell regeneration. PMID: 16972272
- Findings indicate that haplotype variation at the CRHR2 locus is associated with suicidal behavior. PMID: 17532191
- Human myometrium expresses both CRH-R1 and CRH-R2 during pregnancy. PMID: 17959885
- Association of corticotropin-releasing hormone receptor-2 genetic variants with acute bronchodilator response in asthma. PMID: 18408560
- UCN inhibited the proliferation and promoted the apoptosis of endothelial cells and down-regulated VEGF expression in vivo via CRFR2. PMID: 18443956
- Expression loss of CRFR2 in prostate cancer and its neovascularization contributes to prostate tumorigenesis, progression, and neoangiogenesis. PMID: 19058138
- These receptors couple to different G-proteins in stably transfected human cells, leading to transient divalent calcium ion mobilization on top of the natural increase in cyclic AMP stimulation. PMID: 19098121
- The SCP/CRHR2 system is present in human ovaries, and treatment with SCP/Ucn3 inhibits progesterone production by cultured granulosa-lutein cells through interaction with CRHR2. PMID: 19351656
Database Links
Protein Families
G-protein coupled receptor 2 family
Subcellular Location
Cell membrane; Multi-pass membrane protein.
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