CALCRL
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| Location (UCSC) | Chr 2: 187.34 – 187.45 Mb | Chr 2: 84.16 – 84.26 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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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]
Function
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]
- with CGRPreceptor
- with RAMP2: produces an adrenomedullin (AM) receptor, designated AM1[8]
- with RAMP3: produces a dual CGRP/AM receptor designated AM2
These receptors are linked to the
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.,
cardiovascular).[10]
Wounds
In wounds, CGRP receptors found in
botox have been demonstrated to block CGRP cascade, thereby allowing immune system involvement and control of pathogens, resulting in complete control and recovery.[11]
Structure
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
transmembrane helix 5) and TM6 to pivot around TM3 which in turn facilitates Gαs binding.[14]
Adrenomedullin receptor
![[icon]](/File:Wiki_letter_w_cropped.svg){kind=small} | This section is empty. You can help by adding to it. (November 2017) |
Expression
The RNA expression charts show a high level in fetal lung.
| This section needs expansion. You can help by adding to it. (November 2017) |
Clinical significance
Calcitonin gene-related peptide receptor antagonists are approved for the treatment of migraine.
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000064989 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059588 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8626685.
- S2CID 4364526.
- PMID 10354609.
- S2CID 23729715.
- ^ "Receptor properties". SenseLab Project: Membrane properties resource. Yale University. Archived from the original on 2009-02-28. Retrieved 2008-09-28.
- PMID 15464043.
- ^ "How the germ behind flesh-eating disease hijacks neurons to avoid immune destruction".
- PMID 20826335.
- PMID 27566546.
- PMID 28705698.
Further reading
- Born W, Muff R, Fischer JA (2002). "Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP)". Microsc. Res. Tech. 57 (1): 14–22. S2CID 20459079.
- Yallampalli C, Chauhan M, Thota CS, et al. (2003). "Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity". Trends Endocrinol. Metab. 13 (6): 263–9. S2CID 28476322.
- Foord SM, Craig RK (1988). "Isolation and characterisation of a human calcitonin-gene-related-peptide receptor". Eur. J. Biochem. 170 (1–2): 373–9. PMID 2826160.
- Skofitsch G, Jacobowitz DM (1986). "Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system". Peptides. 6 (5): 975–86. S2CID 19435035.
- Flühmann B, Muff R, Hunziker W, et al. (1995). "A human orphan calcitonin receptor-like structure". Biochem. Biophys. Res. Commun. 206 (1): 341–7. PMID 7818539.
- Aiyar N, Rand K, Elshourbagy NA, et al. (1996). "A cDNA encoding the calcitonin gene-related peptide type 1 receptor". J. Biol. Chem. 271 (19): 11325–9. PMID 8626685.
- McLatchie LM, Fraser NJ, Main MJ, et al. (1998). "RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor". Nature. 393 (6683): 333–9. S2CID 4364526.
- Sams A, Jansen-Olesen I (1999). "Expression of calcitonin receptor-like receptor and receptor-activity-modifying proteins in human cranial arteries". Neurosci. Lett. 258 (1): 41–4. S2CID 371196.
- Kamitani S, Asakawa M, Shimekake Y, et al. (1999). "The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells". FEBS Lett. 448 (1): 111–4. S2CID 23729715.
- Aldecoa A, Gujer R, Fischer JA, Born W (2000). "Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells". FEBS Lett. 471 (2–3): 156–60. S2CID 32098863.
- Frayon S, Cueille C, Gnidéhou S, et al. (2000). "Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells". Biochem. Biophys. Res. Commun. 270 (3): 1063–7. PMID 10772950.
- Kuwasako K, Shimekake Y, Masuda M, et al. (2000). "Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling". J. Biol. Chem. 275 (38): 29602–9. PMID 10882736.
- Evans BN, Rosenblatt MI, Mnayer LO, et al. (2000). "CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors". J. Biol. Chem. 275 (40): 31438–43. PMID 10903324.
- Hilairet S, Foord SM, Marshall FH, Bouvier M (2001). "Protein-protein interaction and not glycosylation determines the binding selectivity of heterodimers between the calcitonin receptor-like receptor and the receptor activity-modifying proteins". J. Biol. Chem. 276 (31): 29575–81. PMID 11387328.
- Kamitani S, Sakata T (2001). "Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling". Biochim. Biophys. Acta. 1539 (1–2): 131–9. PMID 11389975.
- Nikitenko LL, Brown NS, Smith DM, et al. (2001). "Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus". Mol. Hum. Reprod. 7 (7): 655–64. PMID 11420389.
- Hilairet S, Bélanger C, Bertrand J, et al. (2001). "Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin". J. Biol. Chem. 276 (45): 42182–90. PMID 11535606.
- Aiyar N, Disa J, Pullen M, Nambi P (2002). "Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells". Mol. Cell. Biochem. 224 (1–2): 123–33. S2CID 26037173.
- Hagner S, Haberberger RV, Overkamp D, et al. (2002). "Expression and distribution of calcitonin receptor-like receptor in human hairy skin". Peptides. 23 (1): 109–16. S2CID 6936664.
- Hill H, Pioszak A (2013). "Bacterial expression and purification of a heterodimeric adrenomedullin receptor extracellular domain complex using DsbC-assisted disulfide shuffling". Protein Expr. Purif. 88 (1): 107–13. PMID 23247088.
External links
- "Calcitonin receptors: CALCRL". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
- calcitonin+receptor-like+receptor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CALCRL human gene location in the UCSC Genome Browser.
- CALCRL human gene details in the UCSC Genome Browser.