Property Summary

NCBI Gene PubMed Count 82
PubMed Score 170.17
PubTator Score 119.06

Knowledge Summary

Patent (9,007)

Expression

  Differential Expression (23)

Disease log2 FC p
astrocytic glioma 3.700 3.9e-04
oligodendroglioma 2.900 2.9e-03
psoriasis -1.300 3.4e-02
glioblastoma 2.400 1.0e-04
osteosarcoma 2.215 4.3e-03
posterior fossa group A ependymoma 1.600 7.1e-06
atypical teratoid / rhabdoid tumor 2.600 2.5e-05
medulloblastoma 1.300 1.2e-03
medulloblastoma, large-cell 2.100 6.0e-05
primitive neuroectodermal tumor 1.400 3.0e-03
tuberculosis -1.500 3.4e-06
non-small cell lung carcinoma -2.400 3.1e-30
intraductal papillary-mucinous adenoma (... -1.300 2.5e-03
intraductal papillary-mucinous carcinoma... -1.400 2.1e-03
intraductal papillary-mucinous neoplasm ... -1.400 1.9e-02
lung cancer -3.600 8.1e-07
interstitial cystitis 2.400 5.4e-05
lung adenocarcinoma -2.300 1.8e-13
pediatric high grade glioma 2.200 2.0e-05
pilocytic astrocytoma 2.200 3.6e-07
lung carcinoma -2.200 1.3e-08
ulcerative colitis 1.500 3.5e-03
ovarian cancer -1.600 4.7e-09

Gene RIF (56)

PMID Text
25982113 Data suggest that ligand binding of a G protein-coupled receptor (GPCR) may inform drug development targeting calcitonin receptor-like receptor (CLR):receptor activity-modifying proteins RAMP1/2 complexes.
25591908 STC1 interferes with CALCRL signaling during osteoblastogenesis via adenylate cyclase inhibition.
24831942 the AM system is widely expressed in human thymus from newborns; both AM1 receptor components CLR and RAMP2, but not RAMP3, are not associated with the plasma membrane of TECs and thymocytes but are located intracellularly, notably in the nucleus
24199627 Data suggest isoforms of RAMP (receptor activity-modifying protein) modulate accessibility of peptides to residues situated on CALCRL N-terminal domain; RAMP3/RAMP2/RAMP1 appear to alter accessibility of specific residues at CALCRL-RAMP interface.
24169318 CRLR expression is upregulated in the fetal lung with increasing gestational age.
24047872 An alanine scan of residues 271-294 of CLR showed that the ability of CGRP to produce cAMP was impaired by point mutations at 13 residues; most of these also impaired the response to adrenomedullin (AM).
23969937 The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis.
23797962 Two CALCRL variants were associated with risk for gestational diabetes.
22933837 The study implicates genetic variation at the CALCRL gene in the pathogenesis of primary angle closure glaucoma in an Australian Caucasian cohort.
22484227 CLR and RAMP1 co-localize in the enteric nervous system of the stomach, ileum and colon, and are in close proximity to their ligands CGRP and IMD
22208649 This study showed that CLR immunoreactivity was observed in satellite glial cells (SGCs) as well as in nerve fibers, but not in neurons.
22142144 human CLR ECL3 is crucial for adrenomedullin (AM)-induced cAMP responses via three CLR/RAMP heterodimers, and activation of these heterodimers probably relies on AM-induced conformational changes
22102369 The CRLR-RAMP2 interactions were confirmed for the full-length proteins on the cell surface by site-specific photo-crosslinking.
21703310 Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function.
20954838 Unexplained infertility was characterised by lower number of vessels stained with CRLR in endometrium compared to fertile controls.
20954838 Observational study of gene-disease association. (HuGE Navigator)
20946927 Structure-function analysis of helix 8 of human calcitonin receptor-like receptor within the adrenomedullin 1 receptor
20424473 Observational study of gene-disease association. (HuGE Navigator)
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20074556 the hCRLR C-tail is crucial for adrenomedullin-evoked cAMP production and internalization of the CRLR/RAMP2, while the receptor internalization is dependent on the aforementioned GPCR kinases, but not Gs coupling.
19913063 Data describe the role of residues 23-60 of the calcitonin receptor-like receptor in binding with interaction sites within the N-terminus of the calcitonin gene-related peptide receptor.
19903822 Activation of calcitonin receptor and calcitonin receptor-like receptor by membrane-anchored ligands.
19898635 The study suggests a possible role of CALCRL in the pathogenesis of acute primary angle closure glaucoma (PACG) but not chronic PACG.
19898635 Observational study of gene-disease association. (HuGE Navigator)
19598235 Observational study of gene-disease association. (HuGE Navigator)
19581316 Intrinsic cardiac adrenergic cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling.
19394311 FACS analysis revealed the crucial CRLR regions (from TM1 to TM5) responsible for cell-surface translocation of receptor activity-modifying proteins.
19210874 findings provided no significant linkage or association of adrenomedullin and CRLR-RAMP-2 genes with rheumatoid arthritis in the studied trio families
19210874 Observational study of gene-disease association. (HuGE Navigator)
18198792 There were some differences in mRNA expression for CL-R (higher) and RAMP3 (lower) in middle cerebral artery compared to coronary artery and pulmonary artery.
17785463 Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor homo-oligomer and a monomer of RAMP1.
17675298 HRS mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor
17503773 A mutated RAMP1 that cannot reach the cell surface, even in the presence of CRLR, indicating that the deficient targeting resulted from the altered conformation of the complex.
17310067 CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates
17067815 Results will facilitate structural analysis of the recombinant protein will facilitate structural analysis of human RCP (receptor component protein), and allow further understanding of RCP function
16622024 adrenomedullin may prevent or reduce rheumatoid arthritis-fibroblast-like synoviocyte apoptosis, via up-regulation of its functional receptor CRLR/receptor activity-modifying protein-2
16495482 Endogenous endothelial CRLR: subcellular localization, internalization and desensitization upon interaction with adrenomedullin and CGRP
16495482 Endogenous CRLR is a key receptor for both adrenomedullin and CGRP in human endothelial cells.
16410241 the respective C-tails of hRAMP2 and -3 differentially affect hCRLR surface delivery and internalization
16293613 Structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general.
15797661 Observational study of gene-disease association. (HuGE Navigator)
15797661 among women, the T allele of the SNP rs696574 (C --> T, in intron 6) was significantly more frequent in essential hypertension subjects
15641806 The N-terminal domain of calcitonin receptor-like receptor is an autonomously folded unit possessing a well-defined structure and is significantly involved in ligand binding and specificity.
15613468 novel function for RAMP3 in the post-endocytic sorting of the calcitonin receptor-like receptor.
15300632 Results demonstrated in the atria of heart failure patients there is an up-regulation of CGRP receptor by an increase of RAMP1 in association with CRLR.
15245870 TNF-alpha induced time- and dose-dependent decreases in the expression of CRLR mRNA in cultured human coronary artery smooth muscle cells, thereby diminishing AM-evoked cAMP production
12824306 Transcriptional regulation of the CRLR gene in microvascular endothelial cells by hypoxia.
12824306 CRLR gene promoter
12684703 findings show that human skin keratinocytes and fibroblasts express adrenomedullin and its receptors L1-R and CRLR
12630808 Cysteine residues in the extracellular loops of hCRLR and in the extracellular domain of hRAMP2 thus appear to play distinct roles in the cell surface expression and function of the receptor heterodimer.
12574158 receptor activity-modifying protein 1 binds to the CRLR
12213903 expression at the human implantation site
11973435 results show the presence of calcitonin receptor-like receptor and receptor activity-modifying proteins in middle meningeal, middle cerebral, pial, and superficial temporal vessels
11937264 The CGRP receptor components, RAMP1 and CRLR, are down-regulated during myeloid differentiation of CD34+ cells, and CGRP receptor selectively promotes the development of CFU-GM.
11814625 This study aimed to identify the cellular location of calcitonin receptor-like receptor (CRLR) which is pharmacologically identical to CGRP receptor-1, a putative molecular target of CGRP and adrenomedullin
11693189 Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells

AA Sequence

MEKKCTLNFLVLLPFFMILVTAELEESPEDSIQLGVTRNKIMTAQYECYQKIMQDPIQQAEGVYCNRTWD      1 - 70
GWLCWNDVAAGTESMQLCPDYFQDFDPSEKVTKICDQDGNWFRHPASNRTWTNYTQCNVNTHEKVKTALN     71 - 140
LFYLTIIGHGLSIASLLISLGIFFYFKSLSCQRITLHKNLFFSFVCNSVVTIIHLTAVANNQALVATNPV    141 - 210
SCKVSQFIHLYLMGCNYFWMLCEGIYLHTLIVVAVFAEKQHLMWYYFLGWGFPLIPACIHAIARSLYYND    211 - 280
NCWISSDTHLLYIIHGPICAALLVNLFFLLNIVRVLITKLKVTHQAESNLYMKAVRATLILVPLLGIEFV    281 - 350
LIPWRPEGKIAEEVYDYIMHILMHFQGLLVSTIFCFFNGEVQAILRRNWNQYKIQFGNSFSNSEALRSAS    351 - 420
YTVSTISDGPGYSHDCPSEHLNGKSIHDIENVLLKPENLYN                                 421 - 461
//

Text Mined References (85)

PMID Year Title
25982113 2015 Structural Basis for Receptor Activity-Modifying Protein-Dependent Selective Peptide Recognition by a G Protein-Coupled Receptor.
25591908 2015 STC1 interference on calcitonin family of receptors signaling during osteoblastogenesis via adenylate cyclase inhibition.
24831942 2014 Expression and distribution of the adrenomedullin system in newborn human thymus.
24199627 2014 Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor: implications for adrenomedullin and calcitonin gene-related peptide pharmacology.
24169318 2014 Adrenomedullin expression in the developing human fetal lung.
24047872 2013 The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.
23969937 2013 The G-protein-coupled receptor CLR is upregulated in an autocrine loop with adrenomedullin in clear cell renal cell carcinoma and associated with poor prognosis.
23797962 2014 Adrenomedullin signaling pathway polymorphisms and adverse pregnancy outcomes.
23597562 2013 Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties.
22933837 2012 A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma.
22484227 2012 Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract.
22208649 2012 Calcitonin gene-related peptide and its receptor components in the human sphenopalatine ganglion -- interaction with the sensory system.
22142144 2012 The third extracellular loop of the human calcitonin receptor-like receptor is crucial for the activation of adrenomedullin signalling.
22102369 2012 Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding.
21703310 2011 Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function.
20954838 2011 Low calcitonin receptor like receptor expression in endometrial vessels from women with unexplained infertility.
20946927 2011 Structure-function analysis of helix 8 of human calcitonin receptor-like receptor within the adrenomedullin 1 receptor.
20826335 2010 Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism.
20596610 2010 Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells.
20424473 2010 L-type voltage-dependent calcium channel alpha subunit 1C is a novel candidate gene associated with secondary hyperparathyroidism: an application of haplotype-based analysis for multiple linked single nucleotide polymorphisms.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20074556 2010 Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 2.
19913063 2010 Mapping interaction sites within the N-terminus of the calcitonin gene-related peptide receptor; the role of residues 23-60 of the calcitonin receptor-like receptor.
19903822 2010 Activation of calcitonin receptor and calcitonin receptor-like receptor by membrane-anchored ligands.
19898635 2009 Investigation of the association between CALCRL polymorphisms and primary angle closure glaucoma.
19598235 2009 Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome.
19581316 2009 Reducing ischaemia/reperfusion injury through delta-opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling.
19394311 2009 Flow cytometric analysis of the calcitonin receptor-like receptor domains responsible for cell-surface translocation of receptor activity-modifying proteins.
19210874 Lack of linkage and association of adrenomedullin and its receptor genes in French Caucasian rheumatoid arthritis trio families.
18240029 2008 Reviews in molecular biology and biotechnology: transmembrane signaling by G protein-coupled receptors.
18198792 2007 Unaltered mRNA expression of calcitonin-like receptor and receptor activity modifying proteins in human arteries in stroke and myocardial infarction.
18039931 2007 Endothelin-converting enzyme-1 regulates endosomal sorting of calcitonin receptor-like receptor and beta-arrestins.
17785463 2007 Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor homo-oligomer and a monomer of receptor activity-modifying protein-1.
17675298 2007 Hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) mediates post-endocytic trafficking of protease-activated receptor 2 and calcitonin receptor-like receptor.
17503773 2007 Assembly and signaling of CRLR and RAMP1 complexes assessed by BRET.
17310067 2007 Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1.
17067815 2007 Overexpression and purification of human calcitonin gene-related peptide-receptor component protein in Escherichia coli.
16622024 2006 A critical role for adrenomedullin-calcitonin receptor-like receptor in regulating rheumatoid fibroblast-like synoviocyte apoptosis.
16495482 2006 Adrenomedullin and CGRP interact with endogenous calcitonin-receptor-like receptor in endothelial cells and induce its desensitisation by different mechanisms.
16410241 2006 Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide and adrenomedullin receptors.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
16293613 2006 The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15797661 2005 Association study of calcitonin-receptor-like receptor gene in essential hypertension.
15641806 2005 Role of the N-terminal domain of the calcitonin receptor-like receptor in ligand binding.
15613468 2005 Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking.
15340161 2004 Signal peptide prediction based on analysis of experimentally verified cleavage sites.
15300632 2004 [Increased atria expression of receptor activity-modifying proteins in heart failure patients].
15245870 2004 Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells.
14722252 2004 Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14668209 2004 Female sex steroid hormones and pregnancy regulate receptors for calcitonin gene-related peptide in rat mesenteric arteries, but not in aorta.
12824306 2003 Transcriptional regulation of the CRLR gene in human microvascular endothelial cells by hypoxia.
12684703 2003 Human skin keratinocytes and fibroblasts express adrenomedullin and its receptors, and adrenomedullin enhances their growth in vitro by stimulating proliferation and inhibiting apoptosis.
12684503 2003 Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity.
12630808 2003 The function of extracellular cysteines in the human adrenomedullin receptor.
12574158 2003 The extracellular domain of receptor activity-modifying protein 1 is sufficient for calcitonin receptor-like receptor function.
12538603 2003 Coexpression of calcitonin receptor-like receptor and receptor activity-modifying protein 2 or 3 mediates the antimigratory effect of adrenomedullin.
12490608 2003 Investigation of CGRP receptors and peptide pharmacology in human coronary arteries. Characterization with a nonpeptide antagonist.
12419522 2002 Paracrine/autocrine function of adrenomedullin in peripheral nerves of rats.
12234182 2002 The transmembrane domain of receptor-activity-modifying protein 1 is essential for the functional expression of a calcitonin gene-related peptide receptor.
12213903 2002 Calcitonin gene-related peptide (CGRP) and CGRP receptor expression at the human implantation site.
12128288 2002 Calcitonin gene-related peptide in pregnancy and its emerging receptor heterogeneity.
12093471 2002 Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells.
12084528 2002 Localization of calcitonin gene-related peptide receptors in rat gastric mucosa.
12036966 2002 Selective inhibition of heterotrimeric Gs signaling. Targeting the receptor-G protein interface using a peptide minigene encoding the Galpha(s) carboxyl terminus.
11973435 2002 Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature.
11937264 2002 Regulation and function of the CGRP receptor complex in human granulopoiesis.
11921352 2002 Functional interaction of G protein-coupled receptors of the adrenomedullin peptide family with accessory receptor-activity-modifying proteins (RAMP).
11693189 2001 Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells.
11535606 2001 Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin.
11420389 2001 Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus.
11389975 2001 Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling.
11387328 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.
10903324 2000 CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.
10882736 2000 Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling.
10772950 2000 Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells.
10767413 2000 Mammalian calcitonin receptor-like receptor/receptor activity modifying protein complexes define calcitonin gene-related peptide and adrenomedullin receptors in Drosophila Schneider 2 cells.
10217420 1999 The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells.
9876047 1998 Expression of calcitonin receptor-like receptor and receptor-activity-modifying proteins in human cranial arteries.
9620797 1998 RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.
8626685 1996 A cDNA encoding the calcitonin gene-related peptide type 1 receptor.
7818539 1995 A human orphan calcitonin receptor-like structure.
3001670 Autoradiographic distribution of 125I calcitonin gene-related peptide binding sites in the rat central nervous system.
2826160 1987 Isolation and characterisation of a human calcitonin-gene-related-peptide receptor.