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calcitonin receptor-like receptor

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Target not currently curated in GtoImmuPdb

Target id: 47

Nomenclature: calcitonin receptor-like receptor

Family: Calcitonin receptors

Quaternary Structure: Complexes
CGRP receptor
AM1 receptor
AM2 receptor
Gene and Protein Information Click here for help
class B G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 461 2q32.1 CALCRL calcitonin receptor like receptor
Mouse 7 463 2 D Calcrl calcitonin receptor-like
Rat 7 464 3q24 Calcrl calcitonin receptor like receptor
Previous and Unofficial Names Click here for help
CLR (unofficial abbreviation in common use) | CRLR
Database Links Click here for help
Specialist databases
GPCRdb calrl_human (Hs), calrl_mouse (Mm), calrl_rat (Rn)
Other databases
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the ectodomain complex of the CGRP receptor
PDB Id:  3N7S
Resolution:  2.1Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human CRLR/RAMP2 extracellular complex
PDB Id:  3AQF
Resolution:  2.6Å
Species:  Human
References:  1
Natural/Endogenous Ligands Click here for help
adrenomedullin, CGRP
Comments: Functional receptor is a dimer of 7TM and RAMP; ligand depends on RAMP
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0003567 abnormal fetal cardiomyocyte proliferation PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0002450 abnormal lymph organ development PMID: 18097475 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0004056 abnormal myocardium compact layer morphology PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0005329 abnormal myocardium layer morphology PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0001191 abnormal skin condition PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0005592 abnormal vascular smooth muscle morphology PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0002190 disorganized myocardium PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0001785 edema PMID: 18097475 
Calcrltm1Kmca|Calcrltm2Kmca|Tg(Tek-cre)12Flv Calcrltm1Kmca/Calcrltm2Kmca,Tg(Tek-cre)12Flv/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J
MGI:1926944  MGI:2136409  MP:0001785 edema PMID: 18097475 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0006207 embryonic lethality during organogenesis PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0002192 hydrops fetalis PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0003222 increased cardiomyocyte apoptosis PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0003288 intestinal edema PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0006208 lethality throughout fetal growth and development PMID: 18097475 
Calcrltm1Kmca|Calcrltm2Kmca|Tg(Tek-cre)12Flv Calcrltm1Kmca/Calcrltm2Kmca,Tg(Tek-cre)12Flv/0
involves: 129P2/OlaHsd * 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J
MGI:1926944  MGI:2136409  MP:0006208 lethality throughout fetal growth and development PMID: 18097475 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0003390 lymphedema PMID: 18097475 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0002188 small heart PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0004057 thin myocardium compact layer PMID: 16537897 
Calcrltm1Kmca Calcrltm1Kmca/Calcrltm1Kmca
129S6/SvEvTac-Calcrl
MGI:1926944  MP:0003814 vascular smooth muscle cell hypoplasia PMID: 16537897 
General Comments
The product of the CALCRL gene, the calcitonin receptor-like receptor alone does not create a functional receptor. Coexpression with receptor activity modifying proteins (RAMPs) allows receptor signal transduction to occur. Reviewed in [2].
Calcitonin receptor-like receptor and RAMP1 make up the CGRP receptor.
Calcitonin receptor-like receptor and RAMP2 make up the AM1 receptor.
Calcitonin receptor-like receptor and RAMP3 make up the AM2 receptor.
The most commonly used abbreviation for this receptor is CLR [2]. At the most recent of the international meetings on CGRP, calcitonin, amylin and adrenomedullin (8th International meeting, Switzerland, 2014), the participants agreed that this should continue to be the preferred abbreviation.
The presence of CLR mRNA does not explain the phenotype of the receptor that is expressed. The expression of RAMP accessory proteins must also be considered.

References

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1. Kusano S, Kukimoto-Niino M, Akasaka R, Toyama M, Terada T, Shirouzu M, Shindo T, Yokoyama S. (2008) Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci, 17 (11): 1907-14. [PMID:18725456]

2. Poyner DR, Sexton PM, Marshall I, Smith DM, Quirion R, Born W, Muff R, Fischer JA, Foord SM. (2002) International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors. Pharmacol Rev, 54 (2): 233-46. [PMID:12037140]

3. ter Haar E, Koth CM, Abdul-Manan N, Swenson L, Coll JT, Lippke JA, Lepre CA, Garcia-Guzman M, Moore JM. (2010) Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure, 18 (9): 1083-93. [PMID:20826335]

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