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CALCRL Membrane Protein Introduction

Introduction of CALCRL

Calcitonin receptor-like receptor (CRL) is a 7-transmembrane family B G protein-coupled receptor for calcitonin gene-related peptide (CGRP). This receptor shares 55% sequence identity with the calcitonin receptor (CTR). CRL is co-expressed with different receptor activity-modifying proteins (RAMPs), which are single-transmembrane accessory proteins regulating the activities of several G protein-coupled receptors. Three types of RAMPs exist in mammals: RAMP1, RAMP2, RAMP3. Co-expression of CRL with RAMP1 results in the in the CGRP receptor, whereas co-expression with RAMP2 or RAMP3 produces the receptor for adrenomedullin, another member of the CGRP family. Besides contributing to receptor specificity, RAMPs are also required for CRLR transportation from the endoplasmic reticulum to the plasma membrane.

Basic Information of CALCRL
Protein Name Calcitonin receptor-like receptor
Gene Name CALCRL
Aliases CGRP type 1 receptor, Calcitonin receptor-like receptor
Organism Homo sapiens (Human)
UniProt ID Q16602
Transmembrane Times 7
Length (aa) 461
Sequence MEKKCTLNFLVLLPFFMILVTAELEESPEDSIQLGVTRNKIMTAQYECYQKIMQDPIQQA
EGVYCNRTWDGWLCWNDVAAGTESMQLCPDYFQDFDPSEKVTKICDQDGNWFRHPASNRT
WTNYTQCNVNTHEKVKTALNLFYLTIIGHGLSIASLLISLGIFFYFKSLSCQRITLHKNL
FFSFVCNSVVTIIHLTAVANNQALVATNPVSCKVSQFIHLYLMGCNYFWMLCEGIYLHTL
IVVAVFAEKQHLMWYYFLGWGFPLIPACIHAIARSLYYNDNCWISSDTHLLYIIHGPICA
ALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFVLIPWRPEGKI
AEEVYDYIMHILMHFQGLLVSTIFCFFNGEVQAILRRNWNQYKIQFGNSFSNSEALRSAS
YTVSTISDGPGYSHDCPSEHLNGKSIHDIENVLLKPENLYN

Functions of CALCRL Membrane Protein

CALCRL receptors are demonstrated to be involved in the pathophysiology of different cardiovascular diseases and migraine. For instance, CALCRL receptors are reported to participate in the regulation of vascular development in maternal and fetal compartments during pregnancy as well as gamete development. CALCRL-null mice die in utero at midgestation with hydrops fetalis and developmental abnormalities in cardiovascular tissues. Secondly, CGRP binds to CALCRL receptors to modulate pain transmission and studies have reported that this receptor plays an important role in the treatment of migraine. Thirdly, in adult mice, the inducible, global genetic deletion of the CALCRL gene causes systemic lymphatic insufficiency in a multitude of lymphatic vascular beds, leading to corneal edema, distal limb edema, and lymphangiectasia.

CALCRL Membrane Protein IntroductionFig.1 CALCRL structure.

Applications of CALCRL Membrane Protein in Literature

1. Mistrova E., et al. Adrenomedullin and the calcitonin receptor-like receptor system mRNA expressions in the rat heart and sensory ganglia in experimentally-induced long-term diabetes. General Physiology & Biophysics. 2014, 33(2): 215-25. PMID: 24177018

This study quantified the expression of the adrenomedullin and the calcitonin receptor-like receptor signaling system in the rat heart and sensory ganglia in streptozotocin-induced long-term diabetes. The results may provide a new possible therapeutic strategy for diabetic cardiomyopathy.

2. Watkins H A., et al. Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor: implications for adrenomedullin and calcitonin gene-related peptide pharmacology. British Journal of Pharmacology. 2014, 171(3): 772-788. PMID: 24199627

This study investigated the mechanism of the interaction of different receptor activity-modifying proteins (RAMPs) with the calcitonin receptor-like receptor (CLR) using mutated receptor models. The results suggested that different RAMPs controlled the accessibility of peptides to binding residues situated on the CLR N-terminus.

3. Tang J Q., et al. The role of caveolae in regulating calcitonin receptor-like receptor subcellular distribution in vascular smooth muscle cells. Biochemistry and Cell Biology. 2013, 91(5): 357-360. PMID: 24032687

Using vascular smooth muscle cell (VSMC) cell line A10, this study investigated the effect of caveolae and caveolin-1 on the distribution of calcitonin receptor-like receptors (CLRs) in VSMC membranes. The results indicated that the structural integrity of caveolae played an important role in regulating subcellular distribution of CLR.

4. Bhargava A., et al. Local injection of dsRNA targeting calcitonin receptor-like receptor (CLR) ameliorates Clostridium difficile toxin A-induced ileitis. Pnas. 2013, 110(2): 731-736. PMID: 23267070

The study investigated the ileum-specific effects of reducing CLR on TxA ileitis by local preinjection of double-stranded RNAs. The results showed that a local injection of the dsRNA targeting CLR could be an effective local therapeutic approach for treating the C.difficile infection.

5. Wang Z., et al. Calcitonin gene-related peptide (CGRP) receptors are important to maintain cerebrovascular reactivity in chronic hypertension. Plos One. 2015, 10(4): e0123697. PMID: 25860809

This article investigated the role of CGPR receptors in cerebral blood flow autoregulation (CA) during chronic hypertension. Study results showed that CGPR receptors played an important role in maintaining cerebrovascular reactivity in chronic hypertension.

CALCRL Preparation Options

As an experienced, reliable, and established service provider of membrane protein solutions, Creative Biolabs now provides a number of customized membrane protein preparation services covering GPCRs, ion channels, membrane transporters, etc. To obtain structurally and functionally intact membrane proteins, we employ different reconstitution systems, including a variety of detergents, membrane mimetics, and lipids, for efficient optimization of the solubilization conditions for your protein of interest. Our experts will give professional advice on the selection of the right format based on your research purposes and further applications. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CALCRL antibody development services.


Supported by our team of experts and the integration of the entire process in our facilities, Creative Biolabs has completed a number of membrane protein-related projects. The full range or single packages of membrane protein services can be offered according to your research demands. contact us to get full advice from our experts to choose the best method for your protein preparation.

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