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FLASH GENE

Symbol

CALCA

contributors: mct - updated : 29-03-2020

HGNC name	calcitonin/calcitonin-related polypeptide, alpha
HGNC id	1437

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	5.69 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	see INS ,PTH PTH

RNA

TRANSCRIPTS	type	messenger

text	calcitonin (3.4kDa) and calcitonin related peptide (3.8kDa) formed by alternative processing

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001741 4 - 840 NP_001732 - 141 - 2008 18603306 NM_001033952 4 - 816 NP_001029124 - 141 - 2008 18603306 NM_001033953 5 - 916 NP_001029125 - 128 - 2008 18603306 NM_001378949 5 - 980 NP_001365878 - 141 - 2008 18603306 NM_001378950 5 - 958 NP_001365879 - 128 - 2008 18603306

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 Digestive liver         Homo sapiens Endocrine thyroid         Nervous brain diencephalon amygdala     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose brown     Homo sapiens Connective adipose white     Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Endocrine thyroid C cell Lymphoid/Immune macrophage Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

isoforms

Precursor

calcitonin (3.4kDa) and calcitonin related peptide (3.8kDa) formed by alternative processing

HOMOLOGY

intraspecies

homolog to calcitonin

Homologene

FAMILY

calcitonin family

CATEGORY

signaling hormone

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,nucleus

basic FUNCTION	involved in calcium homeostasis
	mediating the effects of Indian Hedgehog and PTH related peptide on chondrocyte differentiation
	potent vasodilatator and hypotensor
	acting directly on osteoclasts to inhibit and stimulate osteoclast bone-resorbing activity
	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)
	is a mediator of neurogenic inflammation and the most powerful vasodilating neuropeptide, and has been implicated in migraine pathophysiology
	neuropeptide distributed in bone tissue involved in bone remodeling
	is a strong proangiogenic growth factor, thereby contributing to bone development and remodeling by promoting angiogenesis
	encoding a 37 amino acid neuropeptide, which plays a critical role in the central nervous system
	plays an essential role in synaptic plasticity in the amygdala and fear memory
	may act as a modulator of bone metabolism through osteoblast and osteoclast-associated mechanisms, which result in osteoblast formation with subsequent activation of bone formation
	in addition to its actions in the cardiovascular system, endogenous CALCA is a key regulator of metabolism and energy homeostasis
	induces anorexia, stimulating anorexigenic neuropeptide and/or inhibiting orexigenic neuropeptide expression, through cAMP/PKA pathway activation
	also induces energy expenditure, increasing the skin temperature and brown adipose tissue thermogenesis
	CALCA enhanced HBECs antigen uptake ability and inhibits human bronchial epithelial cells (HBECs) induced T cells proliferation
	contributes to synaptic potentiation in the insular cortex (IC) and plays critical roles in migraine

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text

calcium

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA

RNA

small molecule

protein	TNFSF11 induces the formation of receptors for calcitonin (CALCRL) and CALCA in the bone marrow macrophages (BMM)3)
	CALCRL 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)
	stimulates angiogenesis directly by activating CGRP receptors (CALCR)
	TRPM8 signaling in mucosal sensory neurons is indispensable for the regulation of innate inflammatory responses via the neuropeptide CALCA
	neuronal TRPV1 signaling in periodontal tissue is crucial for the regulation of osteoclastogenesis via the neuropeptide CALCA
	TRPV3 is involved in the local thermoregulatory control of skin blood flow by initiating the release of CALCA peptide and nitric oxide in response to local heating of the skin (
	ADAM17 is involved in the protective effect of CALCA against AGT-induced inflammation via the EGFR-ERK1/2 pathway in Vascular Smooth Muscle Cells
	NGF-induced upregulation of CALCA in orofacial pain induced by tooth movement is dependent on ATP6V0A1, and vesicle release (

cell & other

REGULATION

Other

regulated by USF1 and USF2 (important contributors to neuronal-specific and mitogen-activated protein kinase regulation of the CGRP gene in trigeminal ganglion neurons)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   by hypermethylation of promoter and is a promising prognostic marker and may predict a higher risk for acute lymphoblastic leukemia with central nervous system (CNS) infiltration constitutional     --low   in symptomatic Diverticular disease (DD) patients constitutional     --over   in acute liver failure constitutional     --over   in pre-eclamptic (PE) sera and in PE placentae compared to healthy women

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	CALCA was more valuable than CRP for discriminating between bacteremia and non-bacteremia independent of neutropenia or hematopoietic stem cell transplantation (HSCT)
	serum CALCA is a highly accurate diagnostic test that can be used by physicians for rapid differentiation between bacterial and viral causes of meningitis in adults
	DNA methylation pattern of CALCA in preterm neonates with bacterial sepsis is a putative epigenetic biomarker
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer selective agonists of CALCA may become the potential candidates for treatment of AD neurosensorial visual   may thus be a promising therapeutic agent for the treatment of ocular vascular diseases associated with inflammation

ANIMAL & CELL MODELS

Calca-deficient mice show increased type 2 innate lymphoid cells responses to alarmin (Il33) (