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Tclin Receptor activity-modifying protein 1

Transports the calcitonin gene-related peptide type 1 receptor (CALCRL) to the plasma membrane. Acts as a receptor for calcitonin-gene-related peptide (CGRP) together with CALCRL.

The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N terminus and a cytoplasmic C terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin-gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP1) protein, CRLR functions as a CGRP receptor. The RAMP1 protein is involved in the terminal glycosylation, maturation, and presentation of the CGRP receptor to the cell surface. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]

 Comments

Property Summary

NCBI Gene PubMed Count 52
PubMed Score 142.66
PubTator Score 78.57

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (3)

Disease Target Count Z-score Confidence
Migraine 79 5.702 2.9
Hypertension 293 3.283 1.6

Expression

  Differential Expression (14)

Disease log2 FC p
malignant mesothelioma -1.100 4.5e-06
osteosarcoma 1.041 1.6e-02
sonic hedgehog group medulloblastoma -2.400 1.3e-05
atypical teratoid / rhabdoid tumor -2.600 1.4e-05
medulloblastoma, large-cell -1.600 6.1e-04
primitive neuroectodermal tumor -1.500 9.0e-03
intraductal papillary-mucinous adenoma (... -2.400 5.1e-04
intraductal papillary-mucinous carcinoma... -1.900 6.9e-03
intraductal papillary-mucinous neoplasm ... -1.600 3.1e-02
active ulcerative colitis 1.897 8.2e-03
breast carcinoma 1.700 5.4e-03
interstitial cystitis 1.600 2.4e-03
lung adenocarcinoma 2.200 8.7e-08
ovarian cancer -1.300 3.8e-07

Synonym

Accession O60894 Q6FGS5
Symbols

Gene

RAMP1

PANTHER Protein Class (1)

PDB

3N7P   3N7R   3N7S   4RWG   2YX8  

  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 UniProt Keyword (10)

 GO Function (5)

 GO Component (6)

 GO Process (9)

 Compartment GO Term (26)

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 IMPC Phenotype (2)

 MGI Phenotype (5)

 GWAS Trait (1)

 HCA RNA Cell Line (46)

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Pathway (10)

Protein-protein Interaction (31)

RAMP2   RAMP3   TSHB   CALCA   VIP   GHRH   CALCA   SCT   NPS   TSHR   AVPR2   VIPR1   VIPR2   GLP1R   SCTR   UCN   GNG2   CRHR2   GPR176   PIK3R6   NPSR1   ADM2   GPHB5   GPR150   GPBAR1   RLN3   PIK3R5   PTH2   TAAR1   GPHA2   GPR84  

Drug (1)

Structure of pramlintide

pramlintide
pEC50 9.45

Ligand (1)

Structure of CHEMBL3780091

CHEMBL3780091
pIC50 8.70

Gene RIF (33)

PMID Text
26501962 Evidence that DNA methylation at RAMP1 gene promoter plays a role in migraine was described.
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.
25881990 RAMP1 rs7590387 has a role in the transformation of episodic migraine into medication overuse headache.
24454825 A novel functional role for RAMP1 in regulation of CaSR signalling in addition to its known role in receptor trafficking, is reported.
23867798 multiple NKX3.1 binding sites were found in the RAMP1 locus in human prostate cancer cells and in the normal mouse prostate.
23237777 No significant association of the tested SNPs of the RAMP1 gene were found with migraine susceptibility.
22949393 RAMP1 overexpression enhances the promoting effect that exogenous CGRP has on osteogenic differentiation
22484227 CLR and RAMP1 co-localize in the enteric nervous system of human stomach, ileum, and colon, and are in close proximity to their ligands CGRP and IMD
22208649 The present finding demonstrated that RAMP1 immunoreactivity was localized in many neurons and phenopalatine ganglion.
20933260 lower expression in bronchial biopsies from subjects with asthma
20188075 These data for the first time pinpoint a specific RAMP1 residue important for both antagonist and agonist potency and are consistent with the N-terminal domain of RAMP1 forming the binding pocket interface with calcitonin receptor-like receptor.
20100989 RAMP1 overexpression attenuates Ang-II-induced hypertension and induces a protective change in cardiovascular autonomic regulation
19710695 The T-A-C haplotype is a genetic marker for cerebral infarction, and RAMP1 is associated with increased susceptibility to cerebral infarction.
19710695 Observational study of gene-disease association. (HuGE Navigator)
18725456 the crystal structure of the extracellular domain of human RAMP1 at 2.4 A resolution was determined.
18593822 Identification of RAMP1 residues important for calcitonin gene-related peptide are reported.
18240900 RAMP1 may be strongly considered as a candidate gene for migraine.
18198792 We did not observe any difference in mRNA for CL-R and RAMPs in arteries from patients with hemorrhagic stroke, arteriosclerosis and acute myocardial infarction when compared to patients without these diagnoses
17785463 Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor and RAMP1.
17493758 RAMP1 interacts with tubulin.
17310067 CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-independent mechanisms, where they are degraded at different rates
16912219 This study reveals important functionality of the RAMP C-terminal domain and identifies key differences in the role of the RAMP C terminus for calcitonin receptor versus calcitonin receptor-like receptor-based receptors.
15613468 calcitonin receptor-like receptor heterodimer with RAMP1 yields a calcitonin gene-related peptide receptor
15300632 Data found that expressions of RAMP1, RAMP2 and RAMP3 mRNAs increased with the worsening of heart function, but the expressions of RAMP1 and RAMP2 mRNA decreased at level IV of heart failure.
15245870 TNF-alpha induced time- and dose-dependent decreases in the expression of RAMP1 mRNA in cultured human coronary artery smooth muscle cells, thereby diminishing AM-evoked cAMP production
12684503 identification of domains responsible for agonist binding specificity
12574158 The extracellular domain of receptor activity-modifying protein 1 is sufficient for calcitonin receptor-like receptor function
12565884 Co-expression of calcitonin receptors (CT) lacking a portion of domain 1 with receptor activity-modifying protein (RAMP) 1, 2, or 3 appears to produce functional CT-(8-32)-sensitive adrenomedullin receptors.
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.
11847213 Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists.
11733510 Co-expression of RAMP1 and CRLR reconstituted a CGRP receptor that was able to activate the pheromone-signaling pathway with pharmacological properties similar to those observed previously in mammalian cells.
11693189 Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells

AA Sequence 

MARALCRLPRRGLWLLLAHHLFMTTACQEANYGALLRELCLTQFQVDMEAVGETLWCDWGRTIRSYRELA      1 - 70
DCTWHMAEKLGCFWPNAEVDRFFLAVHGRYFRSCPISGRAVRDPPGSILYPFIVVPITVTLLVTALVVWQ     71 - 140
SKRTEGIV                                                                  141 - 148
//

Text Mined References (53)

PMID Year Title
26501962 2015 DNA methylation of RAMP1 gene in migraine: an exploratory analysis.
25982113 2015 Structural Basis for Receptor Activity-Modifying Protein-Dependent Selective Peptide Recognition by a G Protein-Coupled Receptor.
25881990 2015 Association of RAMP1?rs7590387 with the risk of migraine transformation into medication overuse headache.
24454825 2014 Role of receptor activity modifying protein 1 in function of the calcium sensing receptor in the human TT thyroid carcinoma cell line.
23867798 2013 RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that promotes tumorigenesis.
23251661 2012 Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population.
23237777 2013 Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine.
22949393 2013 The influence of RAMP1 overexpression on CGRP-induced osteogenic differentiation in MG-63 cells in vitro: an experimental study.
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.
20933260 2010 Expression of functional receptor activity modifying protein 1 by airway epithelial cells with dysregulation in asthma.
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.
20188075 2010 Mapping the CGRP receptor ligand binding domain: tryptophan-84 of RAMP1 is critical for agonist and antagonist binding.
20100989 2010 Receptor activity-modifying protein 1 increases baroreflex sensitivity and attenuates Angiotensin-induced hypertension.
19710695 2010 Haplotype-based case-control study of receptor (calcitonin) activity-modifying protein-1 gene in cerebral infarction.
18725456 2008 Crystal structure of the human receptor activity-modifying protein 1 extracellular domain.
18593822 2008 Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function.
18240900 2007 Ramping it up: RAMP1 and the implications for migraine.
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.
17493758 2007 Interaction of receptor-activity-modifying protein1 with tubulin.
17310067 2007 Post-endocytic sorting of calcitonin receptor-like receptor and receptor activity-modifying protein 1.
16912219 2006 A critical role for the short intracellular C terminus in receptor activity-modifying protein function.
15613468 2005 Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
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.
12684503 2003 Identification of the human receptor activity-modifying protein 1 domains responsible for agonist binding specificity.
12574158 2003 The extracellular domain of receptor activity-modifying protein 1 is sufficient for calcitonin receptor-like receptor function.
12565884 2003 Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12446722 2003 Novel receptor partners and function of receptor activity-modifying proteins.
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.
12093471 2002 Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells.
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.
11847213 2002 Receptor activity-modifying protein 1 determines the species selectivity of non-peptide CGRP receptor antagonists.
11754963 2001 The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction.
11733510 2002 Functional expression of heteromeric calcitonin gene-related peptide and adrenomedullin receptors in yeast.
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.
11060459 2000 Genomic structure and chromosome mapping of human and mouse RAMP genes.
10882736 2000 Visualization of the calcitonin receptor-like receptor and its receptor activity-modifying proteins during internalization and recycling.
10385705 1999 Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product.
10354609 1999 RAMPs: accessory proteins for seven transmembrane domain receptors.
9620797 1998 RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.