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FLASH GENE

Symbol

CALCR

contributors: mct/npt - updated : 04-04-2020

HGNC name	calcitonin receptor
HGNC id	1440

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	150.24 kb     13 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
text structure	two regions in the 5prime-flanking sequence that regulated CALCR gene expression in osteoclasts ( both of these putative promoters were responsive to the osteoclast-inducing cytokine, receptor activator of NF-kappaB ligand TNFSF11) (Shen 2007

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001742 14 - 3572 NP_001733 - 474 - 2004 15563840 NM_001164737 16 splicing 3696 NP_001158209 - 508 - 2004 15563840 also called T42D cells lacking 16aa in the first extracellular loop NM_001164738 13 splicing initiation site 3610 NP_001158210 - 474 - 2004 15563840 lacking 16aa as T47D and 47aa in the N terminal extracellular domain variant 4 - splicing 1523 isoform 4 - 290 giant cell tumor 2004 15563840 also called HCTR5 deleted from the putative fourth transmembrane domain to C-tail presence of a previously known 16-aa insert in the putative first intracellular loop variant 5 - splicing 1475 isoform 5 - 274 in giant cell tumor, in TT cells and kidney tissue 2004 15563840 also called HCTR6 deleted from the putative fourth transmembrane domain to C-tail absence of a previously known 16-aa insert in the putative first intracellular loop

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Reproductive female system breast mammary gland     Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective bone       Muscular striatum skeletal   highly

cells

System Cell Pubmed Species Stage Rna symbol Skeleton osteoclast

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	highly in the developing heart

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY	G protein coupled receptor superfamily
	secretin receptor subfamily

CATEGORY

chaperone/stress , receptor

SUBCELLULAR LOCALIZATION

plasma membrane

basic FUNCTION	seven transmembrane segments (7TM) receptor, coupling with Gs alpha protein and activating adenylate cyclase
	calcium-binding chaperone, playing a critical role in the regulation of calcium homeostasis
	regulates calcium metabolism and bone resorption by osteoclasts (Cafforio 2009)
	its expression may contribute to the modulation of cytoplasmic calcium levels needed to regulate T and B cell activation and perhaps other immune functions (Cafforio 2009)
	protects against hypercalcemia predominantly via its inhibitory action on osteoclasts
	physiological role for the CALCR to protect the maternal skeleton during lactation by a direct action on osteocytes to inhibit osteolysis
	CALCR is critical for sustaining quiescence in muscle satellite (stem) cells (MuSCs)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

hormonal

a component

INTERACTION

DNA

RNA

small molecule

protein	RAMP1, RAMP3 inducing specific and high-afffinity binding of amylin (IAPP)
	interacts with GPRASP2
	ligands CALCA and RAMP1, novel class of ligands that activate CR exclusively in an autocrine manner (Chang 2010)
	CALCA stimulates angiogenesis directly by activating CGRP receptors (CALCR)
	CALCR interacts with zonula occludens 1 (TJP1) through PDZ interaction to destabilize tight junctions and increase invasion of prostate cancers (PCs) cells

cell & other

REGULATION

activated by

activated by the peptide hormones calcitonin and amylin

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   from early cardiac development causing an abnormality of the conduction system and cardiac edema

Susceptibility

to bone osteoporosis to Kidney Stone Disease (KSD)

Variant & Polymorphism other	polymorphism associated with bone resorption
	potential association between 3'UTR+18C>T and intron 1 polymorphisms in the CALCR and the risk of kidney stone disease
	rs1801197 could definitely be considered as one of the risk factors for KSD in Indian population

Candidate gene
Marker	high Calcitonin /CALCR expression in primary prostate tumors may serve as a prognostic indicator of disease aggressiveness and poor clinical outcome
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate prevention of CALCR-TJP1 interaction abolishes calcitonin-induced invasion, and can serve as a novel therapeutic tool to treat aggressive prostate cancers

ANIMAL & CELL MODELS