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FLASH GENE

Symbol

CALCRL

contributors: mct - updated : 20-12-2018

HGNC name	calcitonin receptor-like
HGNC id	16709

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminal-CALCRL is structured and further a significant part of the binding affinity comes from binding to the N terminal-domain
	C-tail is crucial for ADM-evoked cAMP production and internalization of the CALCRL/RAMP2

conjugated

GlycoP

HOMOLOGY

interspecies

homolog to murine Calcrl

Homologene

FAMILY

G protein-coupled receptor family 2

CATEGORY

signaling hormone , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,endosome
	intracellular,cytoplasm,organelle,lysosome

basic FUNCTION	can engage signaling partners, such as G proteins and beta-arrestin, following CGRP stimulation, only in the presence of RAMP1
	requires coexpression of different receptor activity modifying proteins (RAMP) to become a functional calcitonin gene-related peptide (CGRP) receptor or an adrenomedullin (AM) receptor
	acts as a receptor for the calcitonin gene-related peptide (CALCA) but in order to recognize CALCA, it must form a complex with an accessory protein, receptor activity modifying protein 1 (RAMP1)
	CALCRL is an important factor in aging and associated disorders
	ADM receptor components CALCRL and RAMP2 gene expression increased with increasing gestational age

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

hormonal

a component	functional CGRP receptors result from the association of a homo-oligomer of the calcitonin receptor-like receptor with a monomer of the accessory protein receptor activity-modifying protein-1 (RAMP1)
	forms a heterodimer with receptor activity-modifying protein 2 (RAMP2)

INTERACTION

DNA

RNA

small molecule

protein	RCP9
	interacting with RAMP1 (requires the assembly of the seven-transmembrane domain calcitonin receptor-like receptor with the single-transmembrane domain receptor activity-modifying prtein-1 to reach the cell surface and be active)
	TNFSF11 induces the formation of receptors for calcitonin (CALCRL)and CALCA in the bone marrow macrophages (BMM)3)
	with RAMP2 serves as the adrenomedullin (AM) receptor to control neovascularization
	CALCA exerts its diverse effects on vasodilation, nociception, secretion, and motor function through a heterodimeric receptor comprising of CALCRL and receptor activity-modifying protein 1 (RAMP1)

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in clear cell renal cell carcinoma, in advanced stages, correlated with high tumor grade and conferred shorter overall survival tumoral     --over   in acute myeloid leukemia with increased mortality

Susceptibility

to essential hypertension to gestational diabetes (GDM)

Variant & Polymorphism SNP	8SNP
	two CALCRL variants were associated with gestational diabetes (GDM) risk

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer urinary   target for future functional studies and drug development in clear cell renal cell carcinoma

ANIMAL & CELL MODELS