Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. [5]
Calcitonin receptor-like (CALCRL), also known as the calcitonin receptor-like receptor (CRLR), is a human protein; it is a receptor for calcitonin gene-related peptide. [5]
The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor. CALCRL is linked to one of three single transmembrane domain receptor activity-modifying proteins (RAMPs) that are essential for functional activity.
The association of CALCRL with different RAMP proteins produces different receptors: [6] [7]
These receptors are linked to the G protein Gs, [9] which activates adenylate cyclase and activation results in the generation of intracellular cyclic adenosine monophosphate (cAMP).
CGRP receptors are found throughout the body, suggesting that the protein may modulate a variety of physiological functions in all major systems (e.g., respiratory, endocrine, gastrointestinal, immune, and cardiovascular). [10]
In wounds, CGRP receptors found in nerve cells deactivate the immune system, to prevent collateral damage in case of a clean wound (common case). In very preliminary research, nerve blockers like e.g. lidocaine or botox have been demonstrated to block CGRP cascade, thereby allowing immune system involvement and control of pathogens, resulting in complete control and recovery. [11]
CALCRL associated with RAMP1 produces the CGRP receptor which is a trans-membrane protein receptor that is made up of four chains. Two of the four chains contain unique sequences. It is a heterodimer protein composed of two polypeptide chains differing in composition of their amino acid residues. The sequence reveals multiple hydrophobic and hydrophilic regions throughout the four chains in the protein. [12]
The CGRP family of receptors including CALCRL can couple to G-protein Gαs, Gαi and Gαq subunits to transduce their signals. Furthermore binding of ligands to CALCRL can bias coupling to these G-protein. [13] Peptide agonist bind to the extracellular loops of CALCRL. This binding in turn causes TM5 (transmembrane helix 5) and TM6 to pivot around TM3 which in turn facilitates Gαs binding. [14]
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The RNA expression charts show a high level in fetal lung.
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Calcitonin gene-related peptide receptor antagonists are approved for the treatment of migraine.
Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH).
Calcitonin gene-related peptide (CGRP) is a member of the calcitonin family of peptides consisting of calcitonin, amylin, adrenomedullin, adrenomedullin 2 (intermedin) and calcitonin‑receptor‑stimulating peptide. Calcitonin is mainly produced by thyroid C cells whilst CGRP is secreted and stored in the nervous system. This peptide, in humans, exists in two forms: CGRP alpha, and CGRP beta. α-CGRP is a 37-amino acid neuropeptide and is formed by alternative splicing of the calcitonin/CGRP gene located on chromosome 11. β-CGRP is less studied. In humans, β-CGRP differs from α-CGRP by three amino acids and is encoded in a separate, nearby gene. The CGRP family includes calcitonin (CT), adrenomedullin (AM), and amylin (AMY).
The calcitonin receptor (CT) is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism.
Adrenomedullin is a vasodilator peptide hormone of uncertain significance in human health and disease. It was initially isolated in 1993 from a pheochromocytoma, a tumor of the adrenal medulla: hence the name.
Receptor activity-modifying proteins (RAMPs) are a class of protein that interact with and modulate the activities of several Class B G protein-coupled receptors including the receptors for secretin, calcitonin (CT), glucagon, and vasoactive intestinal peptide (VIP). There are three distinct types of RAMPs in mammals, designated RAMP1, RAMP2, and RAMP3, each encoded by a separate gene.
Receptor activity modifying protein 1 is a protein that in humans is encoded by the RAMP1 gene.
Receptor activity modifying protein 2, also known as RAMP2, is a protein which in humans is encoded by the RAMP2 gene.
Receptor activity modifying protein 3, also known as RAMP3, is a human gene.
BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene.
Neuropeptide FF receptor 2, also known as NPFF2 is a human protein encoded by the NPFFR2 gene.
Pyroglutamylated RFamide peptide receptor also known as orexigenic neuropeptide QRFP receptor or G-protein coupled receptor 103 (GPR103) is a protein that in humans is encoded by the QRFPR gene.
Neuromedin-U receptor 2 is a protein that in humans is encoded by the NMUR2 gene.
Interleukin 13 receptor, alpha 1, also known as IL13RA1 and CD213A1, is a human gene.
Growth factor receptor-bound protein 14 is a protein that in humans is encoded by the GRB14 gene.
DNA-directed RNA polymerase III subunit RPC9 is an enzyme that in humans is encoded by the CRCP gene.
Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 is an enzyme that in humans is encoded by the PLOD3 gene.
AKT-interacting protein is a protein that in humans is encoded by the AKTIP gene.
Cathepsin F is a protein that in humans is encoded by the CTSF gene.
ADM2 is a protein that in humans is encoded by the ADM2 gene.
GPR182 is a human gene which is an orphan G-protein coupled receptor.